钙离子激活的氯离子通道在慢性鼻窦炎中对黏蛋白MUC5AC表达的调控作用实验研究
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摘要
慢性鼻窦炎是影响人类健康的常见疾病,长期大量流脓涕是困扰患者的一大主要症状。传统的治疗方法如应用抗生素、血管收缩剂、穿刺冲洗等均不能有效改善其长期流脓涕的症状。即使通过鼻内镜手术,改善了鼻窦的引流问题,术后流脓涕的问题仍不能得到有效解决。
慢性鼻窦炎长期流脓涕与鼻窦黏膜中粘蛋白(mucin, MUC)的大量分泌有着密切关系,使其具有“粘液高分泌性疾病”的特点。近年来研究发现,在人呼吸道上皮中钙离子激活的氯离子通道(calcium-activatied chloride channell CaCCl或HCLCAl)参与促进上皮杯状细胞增生,增加MUC5AC的合成。在许多具有“粘液高分泌性疾病”特点的下呼吸道疾病中,如慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)、哮喘、慢性支气管炎等,已发现CaCCl均有特异性的高表达,通过应用CaCCl抑制剂尼弗灭酸(niflumic acid NFA),可以有效抑制呼吸道上皮杯状细胞再生颗粒的产生和MUC5AC的分泌,对这类疾病具有潜在的治疗作用。因此我们设想在慢性鼻窦炎的病理机制中,CaCCl可能同样发挥重要作用,通过对CaCCl的干预,观察能否改善其“高黏液素”的病理环境,从而从新的角度探讨解决其长期流脓涕的问题。因此,对CaCCl在慢性鼻窦炎中对黏蛋白MUC5AC表达的调控作用的关系进行了实验研究,全文由三部分组成：
第一部分钙离子激活的氯离子通道与慢性鼻窦炎关系的研究
目的：观察CaCCl在慢性鼻窦炎和/伴有鼻息肉黏膜中的表达,探讨其在慢性鼻窦炎发病机制中的作用。方法：取Ⅰ型和Ⅱ型慢性鼻窦炎患者筛窦黏膜各10例,另取10例正常筛窦黏膜作为对照。应用Real一time PCR方法检测各组鼻窦黏膜中CaCCl mRNA表达,应用免疫荧光方法观察CaCCl蛋白在各组鼻窦黏膜中的表达情况,比较CaCCl蛋白在各组中平均阳性细胞面积比。结果：CaCClmRNA在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中的表达明显高于对照组(P<0.01),而在两组慢性鼻窦炎组之间差异无统计学意义(P>0.05)。Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜均见杯状细胞增生。CaCCl在两组鼻窦黏膜中均主要表达于上皮杯状细胞,平均阳性细胞面积比在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中差异无统计学意义(P>0.05),而与对照组相比,差异均有统计学意义(P<0.01)。结论：在基因和蛋白水平上,CaCCl在慢性鼻窦炎和/伴有鼻息肉的鼻窦黏膜中均有明显表达,其在慢性鼻窦炎的发病机制中具有重要作用,可能与上皮杯状细胞的增生及粘液高分泌有关。
第二部分黏蛋白5AC与慢性鼻窦炎关系的实验研究
目的：观察MUC5AC在慢性鼻窦炎和/伴有鼻息肉鼻窦黏膜中的表达,探讨其在慢性鼻窦炎病理机制中的作用。方法：实验分组同第一部分,应用real-time PCR方法检测各组鼻窦黏膜MUC5ACmRNA表达,免疫荧光方法观察MUC5AC蛋白在各组鼻窦黏膜中的表达,比较MUC5AC蛋白在各组中平均阳性细胞面积比。结果:MUC5ACmRNA在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中的表达明显高于对照组(P<0.01),而在两组慢性鼻窦炎组之间差异无统计学意义(P>0.05)MUC5AC在两组鼻窦黏膜中均主要表达于上皮杯状细胞,平均阳性细胞面积比在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中差异无统计学意义(P>0.05),而与对照组相比,差异均有统计学意义(P<0.01)。结论：MUC5AC在慢性鼻窦炎和/伴有鼻息肉的鼻窦黏膜中表达明显均增高,MUC5AC在慢性鼻窦炎的发病过程中可能发挥重要作用。
第三部分CaCCl在鼻窦粘膜组织培养中对MUC5AC调控作用的实验研究目的：通过对CaCCl不同方式的干预,观察体外培养的鼻窦粘膜组织中CaCCl及MUC5AC蛋白表达的变化。方法：取鼻内镜手术中切除的筛窦黏膜组织5例,采用组织块培养法培养24小时,每例组织分为5组,A组:培养液不加任何干预；B组：加入人重组TNF-a 10ng/mL；C组：加入NFA(CaCCl抑制刹)10umol/L30分钟后,加入人重组TNF-a10ng/mL;D组:加入NFAl00umol/L30分钟后加入人重组TNF-a 10ng/mL;E组：加入NFA 500umol/L 30分钟后加入人重组TNF-a 10ng/ml。以上5组培养24小时后进行western Blotting实验,观察CaCCl及MUC5AC蛋白在各组织中的表达。结果：TNF-上调CaCCl、MUC5AC蛋白表达水平(p<0.01).CaCCl抑制剂NFA下调CaCCl及MUC5AC蛋白表达(p<0.01),呈剂量依赖效应关系。结论：从蛋白水平上发现,TNF-a诱导的MUC5AC表达在体外培养的筛窦黏膜组织中被CaCCl抑制剂NFA下调。证实了在鼻窦粘膜组织培养中CaCCl对MUC5AC的分泌具有调节作用。
Part I Experimental Studies Of The Relationship Between Calcium-Activatied Chloride Channel 1 And Chronic Rhinosinusitis
Objective:To exmatine the expression of calcium-activatied chloride channe 1 messenger RNA(mRNA) and proteins in human sinus mucosa of chronic rhinosinusitis without nasal polyposis (CRS) and chronic rhinosinusitis with nasal polyposis(CRS/NP). Methods: Ethmoid sinus mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS with and without nasal polyposis and non-CRS pathologies (control).Then sinus mucosa was analyzed using real-time polymerase chain reaction (real-time PCR) to detect the mRNA of calcium-activatied chloride channe 1. Immunofluorescent staining was used to evaluate the expression of calcium -activatied chloride channe 1 proteins in the sinus mucosa. Area ratio of positive cells in the epithelia was compared among the CRS,CRS/NP and the control groups. Results:the mRNA of calcium -activatied chloride channe 1 in the sinus mucosa of CRS and CRS/NP significantly increased compared with that in normal sinus mucosa (p< 0.01). and no significant difference was found between the mucosa of CRS and that of CRS/NP (p>0.05). Calcium-activatied chloride channel 1 proteins were expressed mainly in the goblet cells, hyperplasia of goblet cells were observed in all cases of CRS and CRS/NP. Area ratio of positive cells in the epithelia was found no different between the CRS group and the CRS/NP group (p> 0.05), whereas it was significantly lower in the normal group compared with the other two groups, respectively (p 0.01).Conclusions:This study showed that calcium -activatied chloride channel 1 gene was up-regulated in sinus mucosa of CRS and CRS/NP. Calcium -activatied chloride channel 1 may play an important role in the pathogenesis of CRS and CRS/NP for the over-production of MUC.
Part II Experimental Investagation On The Relationship Between MUC5AC And Chronic Rhinosinusitis
Objective:To investagate the expression of MUC5AC messenger RNA(mRNA) and protein in human sinus mucosa of chronic rhinosinusitis with and without nasal polyposis (CRS and CRS/NP). Methods:Ethmoid sinus mucosa was obtained from patients with CRS with and without nasal polyposis undergoing endoscopic sinus surgery and non-CRS pathologies (control).Then sinus mucosa was analyzed using real-time polymerase chain reaction (real-time PCR) to examine the mRNA of MUC5AC. Immunofluorescent staining was used to evaluate the expression of MUC5AC protein in the sinus mucosa. Area tatios of positive cells in the epithelia were compared among the CRS, CRS/NP and normal groups. Results:Expressions of mRNA of MUC5AC in the sinus mucosa of CRS and CRS/NP significantly increased compared with that in normal sinus mucosa (p< 0.01), and no significant difference was found between the mucosa of CRS and that of CRS/NP (p> 0.05). MUC5AC protein expressed mainly in the goblet cells, hyperplasia of goblet cells was observed in all cases of CRS and CRS/NP. There was no difference of area tatios of positive cells in the epithelia founded between the CRS group and the CRS/NPgroup (p> 0.05), whereas it was significantly lower in the normal group compared with the other two groups, respectively (p< 0.01).Conclusions:These results suggested that MUC5AC gene up-regulatation in sinus mucosa of CRS and CRS/NP may play an important role in the pathogenesis of CRS and NP associated with the hyperplasia of goblet cells and mucin overproduction.
Part III Study Of The Regulation Of Calcium-Activatied Chloride Channel L On MUC5AC Expression In Sinus Mucosa Tissue Culture
Objective:To investigate the regulation of CaCClon MUC5AC expression in sinus mucosa tissue culture. Methods:mucosa (sinus) tissures obtained from patients with chronic rninosinusitis undergoing sinus surgery were cultured for 24 hours.every specimen was divided into 5 groups, A group:maintained in medium without adding any stimulators; group B:added with recombinant human (rh)TNF-a (10 ng/mL); group C:added with CaCC1 inhibitor niflumic acid lOumol/L followed by TNF-a (10 ng/mL) 30 minutes later. group D:added with CaCC1 inhibitor niflumic acid 100 umol/L followed by TNF-a (10 ng/mL) 30 minutes later:group E:added with CaCC1 inhibitor niflumic acid 500 umol/L followed by TNF-a (10ng/mL) 30 minutes later. CaCC1 and MUC5AC protein expressions were quantified by using Western blotting. Results:TNF-a significantly increased CaCCl and MUC5AC proteins expressions in the mucosal explant tissue (P<0.01). Inhibition of CaCC1 with niflumic acid showed a significant dose-dependent reduction of CaCCl and MUC5AC proteins in the mucosal explant tissue (P<.05). Conclusions:TNF-a induced MUC5AC protein expression could be decreased by niflumic acid in explant sinus mucosa tissue which certificated that CaCC1 regulated MUC5AC expression in humann sinus mucosa tissure culture.
慢性鼻窦炎长期流脓涕与鼻窦黏膜中粘蛋白(mucin, MUC)的大量分泌有着密切关系,使其具有“粘液高分泌性疾病”的特点。近年来研究发现,在人呼吸道上皮中钙离子激活的氯离子通道(calcium-activatied chloride channell CaCCl或HCLCAl)参与促进上皮杯状细胞增生,增加MUC5AC的合成。在许多具有“粘液高分泌性疾病”特点的下呼吸道疾病中,如慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)、哮喘、慢性支气管炎等,已发现CaCCl均有特异性的高表达,通过应用CaCCl抑制剂尼弗灭酸(niflumic acid NFA),可以有效抑制呼吸道上皮杯状细胞再生颗粒的产生和MUC5AC的分泌,对这类疾病具有潜在的治疗作用。因此我们设想在慢性鼻窦炎的病理机制中,CaCCl可能同样发挥重要作用,通过对CaCCl的干预,观察能否改善其“高黏液素”的病理环境,从而从新的角度探讨解决其长期流脓涕的问题。因此,对CaCCl在慢性鼻窦炎中对黏蛋白MUC5AC表达的调控作用的关系进行了实验研究,全文由三部分组成：
第一部分钙离子激活的氯离子通道与慢性鼻窦炎关系的研究
目的：观察CaCCl在慢性鼻窦炎和/伴有鼻息肉黏膜中的表达,探讨其在慢性鼻窦炎发病机制中的作用。方法：取Ⅰ型和Ⅱ型慢性鼻窦炎患者筛窦黏膜各10例,另取10例正常筛窦黏膜作为对照。应用Real一time PCR方法检测各组鼻窦黏膜中CaCCl mRNA表达,应用免疫荧光方法观察CaCCl蛋白在各组鼻窦黏膜中的表达情况,比较CaCCl蛋白在各组中平均阳性细胞面积比。结果：CaCClmRNA在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中的表达明显高于对照组(P<0.01),而在两组慢性鼻窦炎组之间差异无统计学意义(P>0.05)。Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜均见杯状细胞增生。CaCCl在两组鼻窦黏膜中均主要表达于上皮杯状细胞,平均阳性细胞面积比在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中差异无统计学意义(P>0.05),而与对照组相比,差异均有统计学意义(P<0.01)。结论：在基因和蛋白水平上,CaCCl在慢性鼻窦炎和/伴有鼻息肉的鼻窦黏膜中均有明显表达,其在慢性鼻窦炎的发病机制中具有重要作用,可能与上皮杯状细胞的增生及粘液高分泌有关。
第二部分黏蛋白5AC与慢性鼻窦炎关系的实验研究
目的：观察MUC5AC在慢性鼻窦炎和/伴有鼻息肉鼻窦黏膜中的表达,探讨其在慢性鼻窦炎病理机制中的作用。方法：实验分组同第一部分,应用real-time PCR方法检测各组鼻窦黏膜MUC5ACmRNA表达,免疫荧光方法观察MUC5AC蛋白在各组鼻窦黏膜中的表达,比较MUC5AC蛋白在各组中平均阳性细胞面积比。结果:MUC5ACmRNA在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中的表达明显高于对照组(P<0.01),而在两组慢性鼻窦炎组之间差异无统计学意义(P>0.05)MUC5AC在两组鼻窦黏膜中均主要表达于上皮杯状细胞,平均阳性细胞面积比在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中差异无统计学意义(P>0.05),而与对照组相比,差异均有统计学意义(P<0.01)。结论：MUC5AC在慢性鼻窦炎和/伴有鼻息肉的鼻窦黏膜中表达明显均增高,MUC5AC在慢性鼻窦炎的发病过程中可能发挥重要作用。
第三部分CaCCl在鼻窦粘膜组织培养中对MUC5AC调控作用的实验研究目的：通过对CaCCl不同方式的干预,观察体外培养的鼻窦粘膜组织中CaCCl及MUC5AC蛋白表达的变化。方法：取鼻内镜手术中切除的筛窦黏膜组织5例,采用组织块培养法培养24小时,每例组织分为5组,A组:培养液不加任何干预；B组：加入人重组TNF-a 10ng/mL；C组：加入NFA(CaCCl抑制刹)10umol/L30分钟后,加入人重组TNF-a10ng/mL;D组:加入NFAl00umol/L30分钟后加入人重组TNF-a 10ng/mL;E组：加入NFA 500umol/L 30分钟后加入人重组TNF-a 10ng/ml。以上5组培养24小时后进行western Blotting实验,观察CaCCl及MUC5AC蛋白在各组织中的表达。结果：TNF-上调CaCCl、MUC5AC蛋白表达水平(p<0.01).CaCCl抑制剂NFA下调CaCCl及MUC5AC蛋白表达(p<0.01),呈剂量依赖效应关系。结论：从蛋白水平上发现,TNF-a诱导的MUC5AC表达在体外培养的筛窦黏膜组织中被CaCCl抑制剂NFA下调。证实了在鼻窦粘膜组织培养中CaCCl对MUC5AC的分泌具有调节作用。
Part I Experimental Studies Of The Relationship Between Calcium-Activatied Chloride Channel 1 And Chronic Rhinosinusitis
Objective:To exmatine the expression of calcium-activatied chloride channe 1 messenger RNA(mRNA) and proteins in human sinus mucosa of chronic rhinosinusitis without nasal polyposis (CRS) and chronic rhinosinusitis with nasal polyposis(CRS/NP). Methods: Ethmoid sinus mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS with and without nasal polyposis and non-CRS pathologies (control).Then sinus mucosa was analyzed using real-time polymerase chain reaction (real-time PCR) to detect the mRNA of calcium-activatied chloride channe 1. Immunofluorescent staining was used to evaluate the expression of calcium -activatied chloride channe 1 proteins in the sinus mucosa. Area ratio of positive cells in the epithelia was compared among the CRS,CRS/NP and the control groups. Results:the mRNA of calcium -activatied chloride channe 1 in the sinus mucosa of CRS and CRS/NP significantly increased compared with that in normal sinus mucosa (p< 0.01). and no significant difference was found between the mucosa of CRS and that of CRS/NP (p>0.05). Calcium-activatied chloride channel 1 proteins were expressed mainly in the goblet cells, hyperplasia of goblet cells were observed in all cases of CRS and CRS/NP. Area ratio of positive cells in the epithelia was found no different between the CRS group and the CRS/NP group (p> 0.05), whereas it was significantly lower in the normal group compared with the other two groups, respectively (p 0.01).Conclusions:This study showed that calcium -activatied chloride channel 1 gene was up-regulated in sinus mucosa of CRS and CRS/NP. Calcium -activatied chloride channel 1 may play an important role in the pathogenesis of CRS and CRS/NP for the over-production of MUC.
Part II Experimental Investagation On The Relationship Between MUC5AC And Chronic Rhinosinusitis
Objective:To investagate the expression of MUC5AC messenger RNA(mRNA) and protein in human sinus mucosa of chronic rhinosinusitis with and without nasal polyposis (CRS and CRS/NP). Methods:Ethmoid sinus mucosa was obtained from patients with CRS with and without nasal polyposis undergoing endoscopic sinus surgery and non-CRS pathologies (control).Then sinus mucosa was analyzed using real-time polymerase chain reaction (real-time PCR) to examine the mRNA of MUC5AC. Immunofluorescent staining was used to evaluate the expression of MUC5AC protein in the sinus mucosa. Area tatios of positive cells in the epithelia were compared among the CRS, CRS/NP and normal groups. Results:Expressions of mRNA of MUC5AC in the sinus mucosa of CRS and CRS/NP significantly increased compared with that in normal sinus mucosa (p< 0.01), and no significant difference was found between the mucosa of CRS and that of CRS/NP (p> 0.05). MUC5AC protein expressed mainly in the goblet cells, hyperplasia of goblet cells was observed in all cases of CRS and CRS/NP. There was no difference of area tatios of positive cells in the epithelia founded between the CRS group and the CRS/NPgroup (p> 0.05), whereas it was significantly lower in the normal group compared with the other two groups, respectively (p< 0.01).Conclusions:These results suggested that MUC5AC gene up-regulatation in sinus mucosa of CRS and CRS/NP may play an important role in the pathogenesis of CRS and NP associated with the hyperplasia of goblet cells and mucin overproduction.
Part III Study Of The Regulation Of Calcium-Activatied Chloride Channel L On MUC5AC Expression In Sinus Mucosa Tissue Culture
Objective:To investigate the regulation of CaCClon MUC5AC expression in sinus mucosa tissue culture. Methods:mucosa (sinus) tissures obtained from patients with chronic rninosinusitis undergoing sinus surgery were cultured for 24 hours.every specimen was divided into 5 groups, A group:maintained in medium without adding any stimulators; group B:added with recombinant human (rh)TNF-a (10 ng/mL); group C:added with CaCC1 inhibitor niflumic acid lOumol/L followed by TNF-a (10 ng/mL) 30 minutes later. group D:added with CaCC1 inhibitor niflumic acid 100 umol/L followed by TNF-a (10 ng/mL) 30 minutes later:group E:added with CaCC1 inhibitor niflumic acid 500 umol/L followed by TNF-a (10ng/mL) 30 minutes later. CaCC1 and MUC5AC protein expressions were quantified by using Western blotting. Results:TNF-a significantly increased CaCCl and MUC5AC proteins expressions in the mucosal explant tissue (P<0.01). Inhibition of CaCC1 with niflumic acid showed a significant dose-dependent reduction of CaCCl and MUC5AC proteins in the mucosal explant tissue (P<.05). Conclusions:TNF-a induced MUC5AC protein expression could be decreased by niflumic acid in explant sinus mucosa tissue which certificated that CaCC1 regulated MUC5AC expression in humann sinus mucosa tissure culture.
引文
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13. Voynow J AS, Ellby MR, Mose MC. Muein gene expression (MIC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fihrosis, allergic rhinitis, and normal individuals, Lung.1998,176:345-54
14 Ali MS, Hutton DA, Wilson JA, et al.Major secretory mucin expression in chronic sinusitis. Otolaryngol Head Neck Surg,2005,133(3):423-428
15 Kim DH, Chu HS, Lee JY, et al. Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg,2004,130(6):747-752.
16 Jung HH, Lee JH, Kim YT, et al. Expression of mucin genes in chronic ethmoiditis. Am J Rhinol,2000,14(3):163-170.
17 Mattew E. Loewen George W. Forsyth Structure and function of CLCA Proteins Physiol Rev 2005;(85):1061-1092,
18Nakanishi A, Morita S, Iwashita H, et al. Role of gob5 in mucus overproduction and airway hyperesponsiveness in asthma. Proc Natl Acad Sci USA,2001;98(9):5175-5180.
19 Makoto H, Shigeru M, Hiroki I, et al. Increased expression of the human Ca2+-activated Cl- channel 1 (HCLCA1) gene in the asthmatic airway. Am J Respir Crit Care Med,2002(165):1322-1136.
20 Ke Wang, Fu Qiang Wen, et al. Increased expression of human calcium-activated chloride channel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway Cell Biology International.2007;(31) 1388-1395
21宋立强,戚好文,等.钙激活氯离子通道在气道杯状细胞合成黏蛋白中的促进作用.第四军医大学学报.2004,25(16):1470-1473
22 Hegah AE, Sakamoto T, Uchida Y, et al. CLCA1 gene polymorphisms in chronic obstructive pulmonary disease.J Med Genetics,2004, (41):e27.
23 Hoshino M, Morha S, Shlha H. Role of gob-5 in mucus overproduction and airway hyperresponsivernessinasthma [J]. ProcNatf Acad Sci USA,2001,98 (9):5175-5180
24 Zhou Y, Dong Q, Louahed J, et al.IICLCA1:a novel IL-9 induced chloride channel on airway epithelial that is responsible for mucus production. Am J Respir Crit Care Med,2000,161(5):597-601.
25 Paula J. Busse, Teng Fei Zhang, et al. Chronic exposure to TNF-a increases airway mucus gene expression in vivo. J Allergy Clin Immunol 2005, 116(6):1256-1262
26 Ahmed E. Hegab G, Tohru Sakamoto,et al. Niflumic acid and AG-1478 reduce cigarette Smoke-Induced Mucin Synthesis. The Role of hCLCAl. CHEST 2007,131 (4) 1149-1156
1 Nakanishi A,Morita S,Iwashi ta H,et al.Role of gob5 in mucus overproduction and airway hyperesponsi veness in asthma.Proc Natl Acad Sci USA,2001,98(9):5175-5180.
2Hoshino M,Morita S,Iwashi ta H,et al. Increased expression of the human Ca2-activated cl-channel 1 (CaCCl)gene in the asthmatic airway.[J],Am J Respir Cri t Care Med,2002,165(8):1132-113
3宋立强.戚好文等.钙激活氯离子通道在气道杯状细胞合成黏蛋白中的促进作用第四军医大学学报,2004,25(16)1470-1473
4Ke Wang,Fu Qiang Wen,et al.Increased expression of human calcium-activated chloridechannel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway. Cell Biology International,2007,31:1388-1395
5 Toda M, Tulic MK, Levitt RC, et al. A calcium-activated chloride channel (HCLCAl)is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma [J].J Allergy Clin Immunol,2002,109(2):246-250.
6 PeterJ, Barnes M. Emerging Targets for COPD Therapy.Current Drug Targets Inflammat ion Allergy,2005,4:675-683
7Hauber HP,John J,Lily H.P.Increased expression of interleukin-9, interleukin一9 receptor, and the calcium-acti vated chl ori de channel(hclcal) in the upper airways of patients with cystic fibrosis. Laryngoscope, 2003,(125)1137-1142
8 Paula.J.Busse,H, Teng Fei Zhang,et al.Chronic exposure to TNF-a increases airway mucus gene expression in vivo.J Allergy Clin Immunol,2005,116 (6):1256-1262
9Yu hong Zhou, Qu Dong, Louahed J,et al. Characterization of a cal cium-activated chloride channelas a shared target of th2 cytokine pathways and its potential involement in asthma. Am J Respir Cell Mol Biol, 2001,25:,486-491
10Masanori Yasuo,Keisaku Fujimoto,Tsuyoshi Tanabe et al. Relationship hetween calcium-activated chloride channel 1 and muc5ac in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells. Respiration,2006,73:347-359
11Ahmed E.Henab,Tohru Sakamoto,et al. niflumic acid and AG-1478 reduce igarette.smole-induced mucin synthesis.the role of helcal.CHEST,2007,131 (4):1149-1156
12Bachert C, Cauwenberge V. Inflammatory mechanisms in chronic sinusitis. Acta Otorhinolaryngol Belg,1997,51(4):209-217.
13Mullol J, Xaubet A, Lopez E,. Comparative study of the effects of different glucocorticosteroids on eosinophil survival primed by cultured epithelial cell supernatants obtained from nasal mucosa and nasal polyps. Thorax, 1995,50 (3):270-274.
14Ming YG, Rhee CS. Inflammatory cytokine expression on nasal polyps developed in allergic and infectious rhinitis. Acta Otolaryngol Suppl.1997,117:302.
15 Ragab A, Clement P, Vincken W. Fungal cultures of different parts of the upper and lower airways in chronic rhinosinusitis.Rhinology, 2006,44(1):19-25.
16Hauber HP, Daigneaul TP, FREN KS, et al. Niflumic acid and MSI22216 reduce TNF-α induced mucin expression in human airway mucosa.J Allergy Clin Immunol,2005,115:266-271.
17Hauber HP, Steffen A, GoldmannT et al. Effect of steroids, acetyl-cysteine and calcium-activated chloride channel inhibitors on allergic mucin expression in sinus mucosa. Laryngoscope,2008,118:1528-1533
1 Duncan F, Rogers M.Airway mucus hypersecretion in asthma:an undervalued pathology? Current Opinion in Pharmacology 2004, (4):241-250
2 Alan D.Jackson H. Airway goblet-cell mucus secretion. TRENDS in Pharmacological, Sciences,2001, (22):39-45
3 Shale DJ, Ionescu AA, Mucus hypersecretion:a common symptom, a common mechanism? Eur Respir J,2004,23:797-798
4 Mahmoud S, Ali MS, Jeffrey P. Upper Airway Mucin Gene Expression:A Review Laryngoscope,2007,117:932-938
5 Philip Thai, Yin Chen, Gregory D, et al. differential regulation of muc5ac /muc5ac and hclca-1/mgob-5 expression in airway epithelium. Am J Res Cell Molecular Biol.2005,33:524-530
6 Ali MS, Huton D A, Wilson JA, et al. Major secretory mucin expression in chronic sinusitis. Otolaryngol Head Neck Surg,2005,133:423-428.
7 Kim CH, Chu HS, Lee JY, et al. U Expression of MUC5AC mRNA in the goblet cells of human nasal mucosa. Laryngoscope,2000,110:2110-2113
8 Burgel PR, Escudier E, Coste A, Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps. J Allergy Clin Immunol,2000,106:705-712
9 Kim CH, Song MS, Kim SS. Expression of muc5ac mrna in the goblet cells of human nasal mucosa. Laryngoscope,2000,110:2110-2113
10Groneberg DA, PeiserC, Dinh QT, et al. Distribution of respiratory mucin proteins in human nasal mucosa. Laryngoscope,2003:113:520-524.
11Jung HH, Lee JH, Kim YT. et al.. Expression of mucin genes in chronic et hmoiditis. Am J Rhinoi 2000,14:163-70
12 Maria TP, Pawandeep K, Aujla MS. Immunohistochemical analyses of muc5ac mucin expression in sinus mucosa of chi ldren wi th sinusi t is and controls. Ann otology Larynagology.2005,114(12):958-965.
13 SeongJK, K00 JA, LEE WJ. Upregulation of MUC8 and downregulation of muc5ac by inflammatory mediators in human nasal polyps and cultured nasal epi thelium. Acta Otolaryngol,2002,122:401-407
14 Hauber HP, Daigneaul TP,FREN KS, et al. Niflumic acid and MSI22216 reduce TNF-α induced mucin expression in human airway mucosa. J Allergy Clin Immunol,2005,115:266-271.
15 Temann L'A, Prasad B, Gallup MW, et al. A novel role for murine (?)-4 in vive induction of MUC5AC gene expression and mucin hypersecretion. Am J Respir Cell mol Biol,1997,16:471-478
16 Zhou Y, Dong Q, Louahed J, et al. HCLCA1:a novel IL-9 induced chloride channel on airway epithelial that is responsible for mucus production. Am J Respir Crit Care Med,2000,161(5):597-601.
17 Kook KJ, Hoon KC, Kim K, et al. Effects of prostaglandin E(2)on gel-forming Mucin secretion in normal human nasal epithelial cells. Acta Otolaryngol,2 006,126(2):174-179.
18 Matsu KS,Stel AC, Georas SN, et al.Interleukin-13 up-regulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism[J], Am J Respir Cell Mol Biol,2001,24:755-762.
1 Nakanishi A, Morita S, Iwashita H, et al. Role of gob5 in mucus overproduction and airway hyperesponsiveness in asthma. Proc Natl Acad Sci USA,2001,98 (9):5175-5180.
2 Makoto H, Shigeru M,Hiroki I, et al. Increased expression of the human Ca2 +-activated Cl- channel 1 (HCLCAl) gene in the asthmatic airway. Am J Respir Crit Care Med,2002(165):1322-1136.
3 Zhou Y, Dong Q, Louahed J, et al. HCLCA1:a novel IL-9 induced chloride channel on airway epithelial that is responsible for mucus production. Am J Respir Crit Care Med,2000,161 (5):5972601.
4 Paula J, Busse, M, Teng Fei Zhang, et al. Chronic exposure to TNF-a increases airway mucus gene expression in vivo.J Allergy Clin Immunol,2005,116, (6):1256-1262
5 Ahmed E,Hegab, Tohru Sakamoto, et al. Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis the role of hCLCAl. CHEST,2007,131 (4): 1149-1156
6 Hauber IIP, Daigneaul t P, Frenkiel S, Niflumic acid and MSI-2216 reduce TNF-a-induced mucin expression inhuman airway mucosa. J Allergy Clin Immunol 2005:115:266-271
7 Hauber HP,Steffen A,Goldmann T, Effect of steroids, acetyl-cysteine and calcium-activated chloride channel inhibitors on allergic mucin expression in sinus mucosa. The Laryngoscope,2008,118:1528-1533
8彭璐,甄宏韬,龙小博等.地塞米松和组胺对人鼻息肉组织黏蛋白MUC5AC mRNA和蛋白表达的影响.临床耳鼻咽喉头颈外科.2007,21：926 928
9 Levine SJ, Larivee P, Logun C, et al. Tumor necrosis factor-alpha induces mucin hypersecretion and MUC2 gene expression by human airway epithelial cells. Am J Respir Cell Mol Biol,1995,12:196-204.
10 Song KS, Lee WJ, Chung KC, et al. Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in humane airway epithelial cells,J Biol Chem,2003,278:24243-50.
11Takeyama L, Dabbagh K, Lee HM, et al. Epidermal growth factor receptor system regulate Mucin production in airways. Proc Natl Acad Sci USA.1999,96:3081-6
12 Masanori Yasuo, Keisaku Fujimoto, Tsuyoshi Tanabe, et al. Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells. Respiration,2006,73:347-59
13 Guohua Zhen, Park SW,Louis T, et al. IL-13 and Epidermal growth factor receptor have critical but distinct roles in epithelial cell mucin production. Am J Respir Cell Mol Biol,2007,36:244-253
14 Kim YD, Kwon EJ, Park DW, et al. Interleukin-lbeta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol 2002;62:1112-8.
15 Barnett J, Chow J, Ives D, et al. Purification, characterization and selective inhibition of human prostaglandinG/H synthase 1 and 2 expressed in the baculovirus system. Biochim Biophys Acta,1994,324:26-34.
l.Jefery PK, Li D. Airway mucosa:secretory cells, mucus and mucins. Eur Respir J,1997,10(7):1655-1662
2. Moniaux N, Escande F, Porchet N, et al.Structural organization and classification Of the human mucin genes. Front Biosci,2001,6:D1192-D1206.
3. Dekker J, Rossen JW, Buller HA, et al. The MUC family:an obituary. Trends Biochem Sci,2002,27(3):126-131.
4. Voynow JA. What does mucin have to do with lung disease? Paediatr Reapir rev.2002:3:98-103.
5 Williams SJ, Wreschner DH, Tra M, et al. A MUC13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells. J Biol Chem,2001,27 6(21):18327-18336.
6. Pallesen LT, Berglund L, Rasmussen LK, et al. Isolation and characterization of MUC15, a novel cell membrane-associated mucin. Eu r J Bio chem, 2002,269(11):2755-2763
7. Chen Y, Zhao YH, Kalaslavadi TB, et al. Genome-wide search and identification of a novel gel-forming mucin MUC19/Mucl9 in glandular tissues. Am J Respir Cell Mol Bio,2004,30(2):155-165.
8. Ordonez CL, Khashayar R, Wong HH, et al. Mild and moderate asthma is associated with airway goblet cell metaplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Mod.2001,163:517-523
9. Takeyama K,Fahy JV,Nadel JA. Realtionship of epidermal growth factor receptors To airway goblet cell production. Am J Respir Crit Care Med. 2001,163:511-6.
10. Sharma P, Dudus L, Nielsen PA, et al. MUC5B and MUC7 are diferentially expressed in mucous and serous cells of submucosal glands in human bronchial airways. Am J Respir Cell Mol Biol,1998,19:30-37
11. Lamblin G, Degroote S, Perini JM, et al. Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis. Glycoconj J,2001,18:661-684.
12. Groneberg DA, Eynott PR, Lim S, et al. Expression of respiratory mucins in fatalstatus asthmaticus and mild asthma. Histopathoiogy,2002,40:367-373.
13. Voynow J A, Sollby DM, Rose MC. M uci ng enee xpression (MUCI, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fibrosis, allergic rhinitis, and normal individuals. Lung,1998,176:345-54
14 Gandhi R, Elble RC, Gruber AD, et al. M olecular and functional characterization of A calcium-sensitive chloride channel from mouse lung[J].J Biol Chem,1998,273(48):32096-32101.
15 Mattew E, Loewen W, Georgy W. Structure and function of CLCA proteins. Physiol Rev,2005,85:1061-1092
16 Leverkoehne I, Gruber AD. The murine mCLCA3(Alias gob-5)protein is located in the mucin granule membranes of intestinal, respiratory, and uterine goblet cells[J].J Histochem Cytochem,2002,50(6):829-838
17 Gruber AD, Elble RC, Ji HL, et al. Genomic cloning.molecular characterization, and functional analysis of human HCLCA1, the first human member of the family of Ca2 activated C12 channelproteins. Genomics,1998;54(2):200-214.
18 Hegab AE, Sakamoto T, Uchida Y, et al. CLCA1 gene polymorphisms in chronic obstructive pulmonary disease. J Med Genetics,2004(41):e27
19 Hoshino M, Morha S, Shlha H. Role gob-5 in mucus overproduction and airway hypcrresponsiverness in asthma [J]. ProcNatf Acad Sci USA,2001:98(9)5175-5180
20 Zhou Y, Dong Q, Louahed J, et al. HCLCA1:a novel IL-9 induced chloride channel on airway epithelial that is responsible for mucus production. Am J Respir Crit Care Med,2000,161 (5):597-601.
21 Paula J, Busse, Teng Fei Zhang, et al. Chronic exposure to TNF-a increases airway mucus gene expression in vivo.J Allergy Clin Immunol,2005,116 (6):1256-1262
22 Ahmed E, Hegab M, Tohru Sakamoto, et al. Niflumic acid and AG-1478 reduce cigarette Smoke-Induced Mucin Synthesis The Role of hCLCA1 CHEST 2007,131 (4) 1149-1156
23 Nakanishi A, Morita S, Iwashita H, et al. Role of gob5 in mucus overproduction and airway hyperesponsiveness in asthma. Proc Natl Acad Sci USA,2001,98 (9):5175-5180.
24 Alimam M, Piazza F.M, Selby DM, et a. Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways. Am J Respir Coll Mol Biol.2000,22(3):253-260
25Ke Wang, FuQiang Wen, et al. Increased expression of human calcium-activated chloridochannel 1 gene is correlated with mucus overproduction in Chinese sthmatic airway Cell Biology International,2007(31):1388-1395
26宋立强.戚好文等.钙激活氯离子通道在气道杯状细胞合成黏蛋白中的促进作用第四军医大学学报,2004,25(16)1470-1473
27 Toda M, Tulic, Levitt RC.A calcium-activated chloride channel (HCLCAI) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma [J] J Allergy clin Immunol.2002,109(2):246 —250.
28 Wilk JB,Destefano AL, Aenett DK, et al.A genome—wide scan of pulmonary function measures in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Respir Crit Care Med,2003,167 (11):1528-1533.
29 Silverman EK, Palmer LJ,Mosley JD, et al. Genome-wide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary diseases. Am J Hum Genet,2002,70(5):1229-1239.
2. Moniaux N, Escande F, Porchet N, et al. Structural organization and classification Of the human mucin genes. Front Biosci.2001,6:D1192-D1206.
3. Dekker J, Rossen J, Buller HA, et al. The MUC family:an obituary. Trends Biochem Sci.2002,27(3):126-131.
4. Voynow JA. What does mucin have to do with lung disease? Paediatr Reapir rev.2002:3:98-103.
5 Williams SJ, Wreschner DH, Tra M, et al. A Mucl3, a novel human cell surface mucin expressed by epithelial and hemopoietic cells. J Biol Chem, 2001,276(21):18327-18336.
6. Pallesen LT, Berglund L, Rasmussen LK, et al.. Isolation and characterization of MUC15, a novel cell membrane-associated mucin. Eur J Biochem, 2002,269(11):2755-2763
7. ChenY, Zhao YH, Kalaslavadi TB, et al.Genome-wide search and identification of a novel gel-forming mucin MUC19/Mucl9 in glandular tissues. Am J Respir Cell Mol Bio,2004,30(2):155-165.
8. Ordonez CL, Khashayar R, Wong HH, et al. Mild and moderate asthma is associated with airway goblet cell metaplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med,2001,163:517-523
9.Takeyama K,Fahy JV, Nadel JA. Realtionship of epidermal growth factor receptors to airway goblet cell production. Am J Respir Crit Care Mod.2001,163:511-516.
10. Sharma P, Dudus L, Nielsen PA, et al. MUC5B and MUC7 are diferentially expressed in mucous and serous cells of submucosal glands in human bronchial airways. Am J Respir Cell Mol Biol.1998,19:30-37
11. Lamblin G, Degroote S, Perini JM, et al. Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis Glycocon J,2001,18:661-684.
12. Groneberg DA, Eynott PR, Lim S, et al.Expression of respiratory mucins in fatal Status asthmaticus and mild asthma. Histopathology,2002,40:367-73.
13. Voynow J AS, Ellby MR, Mose MC. Muein gene expression (MIC1, MUC2, and MUC5/5AC) in nasal epithelial cells of cystic fihrosis, allergic rhinitis, and normal individuals, Lung.1998,176:345-54
14 Ali MS, Hutton DA, Wilson JA, et al.Major secretory mucin expression in chronic sinusitis. Otolaryngol Head Neck Surg,2005,133(3):423-428
15 Kim DH, Chu HS, Lee JY, et al. Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg,2004,130(6):747-752.
16 Jung HH, Lee JH, Kim YT, et al. Expression of mucin genes in chronic ethmoiditis. Am J Rhinol,2000,14(3):163-170.
17 Mattew E. Loewen George W. Forsyth Structure and function of CLCA Proteins Physiol Rev 2005;(85):1061-1092,
18Nakanishi A, Morita S, Iwashita H, et al. Role of gob5 in mucus overproduction and airway hyperesponsiveness in asthma. Proc Natl Acad Sci USA,2001;98(9):5175-5180.
19 Makoto H, Shigeru M, Hiroki I, et al. Increased expression of the human Ca2+-activated Cl- channel 1 (HCLCA1) gene in the asthmatic airway. Am J Respir Crit Care Med,2002(165):1322-1136.
20 Ke Wang, Fu Qiang Wen, et al. Increased expression of human calcium-activated chloride channel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway Cell Biology International.2007;(31) 1388-1395
21宋立强,戚好文,等.钙激活氯离子通道在气道杯状细胞合成黏蛋白中的促进作用.第四军医大学学报.2004,25(16):1470-1473
22 Hegah AE, Sakamoto T, Uchida Y, et al. CLCA1 gene polymorphisms in chronic obstructive pulmonary disease.J Med Genetics,2004, (41):e27.
23 Hoshino M, Morha S, Shlha H. Role of gob-5 in mucus overproduction and airway hyperresponsivernessinasthma [J]. ProcNatf Acad Sci USA,2001,98 (9):5175-5180
24 Zhou Y, Dong Q, Louahed J, et al.IICLCA1:a novel IL-9 induced chloride channel on airway epithelial that is responsible for mucus production. Am J Respir Crit Care Med,2000,161(5):597-601.
25 Paula J. Busse, Teng Fei Zhang, et al. Chronic exposure to TNF-a increases airway mucus gene expression in vivo. J Allergy Clin Immunol 2005, 116(6):1256-1262
26 Ahmed E. Hegab G, Tohru Sakamoto,et al. Niflumic acid and AG-1478 reduce cigarette Smoke-Induced Mucin Synthesis. The Role of hCLCAl. CHEST 2007,131 (4) 1149-1156
1 Nakanishi A,Morita S,Iwashi ta H,et al.Role of gob5 in mucus overproduction and airway hyperesponsi veness in asthma.Proc Natl Acad Sci USA,2001,98(9):5175-5180.
2Hoshino M,Morita S,Iwashi ta H,et al. Increased expression of the human Ca2-activated cl-channel 1 (CaCCl)gene in the asthmatic airway.[J],Am J Respir Cri t Care Med,2002,165(8):1132-113
3宋立强.戚好文等.钙激活氯离子通道在气道杯状细胞合成黏蛋白中的促进作用第四军医大学学报,2004,25(16)1470-1473
4Ke Wang,Fu Qiang Wen,et al.Increased expression of human calcium-activated chloridechannel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway. Cell Biology International,2007,31:1388-1395
5 Toda M, Tulic MK, Levitt RC, et al. A calcium-activated chloride channel (HCLCAl)is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma [J].J Allergy Clin Immunol,2002,109(2):246-250.
6 PeterJ, Barnes M. Emerging Targets for COPD Therapy.Current Drug Targets Inflammat ion Allergy,2005,4:675-683
7Hauber HP,John J,Lily H.P.Increased expression of interleukin-9, interleukin一9 receptor, and the calcium-acti vated chl ori de channel(hclcal) in the upper airways of patients with cystic fibrosis. Laryngoscope, 2003,(125)1137-1142
8 Paula.J.Busse,H, Teng Fei Zhang,et al.Chronic exposure to TNF-a increases airway mucus gene expression in vivo.J Allergy Clin Immunol,2005,116 (6):1256-1262
9Yu hong Zhou, Qu Dong, Louahed J,et al. Characterization of a cal cium-activated chloride channelas a shared target of th2 cytokine pathways and its potential involement in asthma. Am J Respir Cell Mol Biol, 2001,25:,486-491
10Masanori Yasuo,Keisaku Fujimoto,Tsuyoshi Tanabe et al. Relationship hetween calcium-activated chloride channel 1 and muc5ac in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells. Respiration,2006,73:347-359
11Ahmed E.Henab,Tohru Sakamoto,et al. niflumic acid and AG-1478 reduce igarette.smole-induced mucin synthesis.the role of helcal.CHEST,2007,131 (4):1149-1156
12Bachert C, Cauwenberge V. Inflammatory mechanisms in chronic sinusitis. Acta Otorhinolaryngol Belg,1997,51(4):209-217.
13Mullol J, Xaubet A, Lopez E,. Comparative study of the effects of different glucocorticosteroids on eosinophil survival primed by cultured epithelial cell supernatants obtained from nasal mucosa and nasal polyps. Thorax, 1995,50 (3):270-274.
14Ming YG, Rhee CS. Inflammatory cytokine expression on nasal polyps developed in allergic and infectious rhinitis. Acta Otolaryngol Suppl.1997,117:302.
15 Ragab A, Clement P, Vincken W. Fungal cultures of different parts of the upper and lower airways in chronic rhinosinusitis.Rhinology, 2006,44(1):19-25.
16Hauber HP, Daigneaul TP, FREN KS, et al. Niflumic acid and MSI22216 reduce TNF-α induced mucin expression in human airway mucosa.J Allergy Clin Immunol,2005,115:266-271.
17Hauber HP, Steffen A, GoldmannT et al. Effect of steroids, acetyl-cysteine and calcium-activated chloride channel inhibitors on allergic mucin expression in sinus mucosa. Laryngoscope,2008,118:1528-1533
1 Duncan F, Rogers M.Airway mucus hypersecretion in asthma:an undervalued pathology? Current Opinion in Pharmacology 2004, (4):241-250
2 Alan D.Jackson H. Airway goblet-cell mucus secretion. TRENDS in Pharmacological, Sciences,2001, (22):39-45
3 Shale DJ, Ionescu AA, Mucus hypersecretion:a common symptom, a common mechanism? Eur Respir J,2004,23:797-798
4 Mahmoud S, Ali MS, Jeffrey P. Upper Airway Mucin Gene Expression:A Review Laryngoscope,2007,117:932-938
5 Philip Thai, Yin Chen, Gregory D, et al. differential regulation of muc5ac /muc5ac and hclca-1/mgob-5 expression in airway epithelium. Am J Res Cell Molecular Biol.2005,33:524-530
6 Ali MS, Huton D A, Wilson JA, et al. Major secretory mucin expression in chronic sinusitis. Otolaryngol Head Neck Surg,2005,133:423-428.
7 Kim CH, Chu HS, Lee JY, et al. U Expression of MUC5AC mRNA in the goblet cells of human nasal mucosa. Laryngoscope,2000,110:2110-2113
8 Burgel PR, Escudier E, Coste A, Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps. J Allergy Clin Immunol,2000,106:705-712
9 Kim CH, Song MS, Kim SS. Expression of muc5ac mrna in the goblet cells of human nasal mucosa. Laryngoscope,2000,110:2110-2113
10Groneberg DA, PeiserC, Dinh QT, et al. Distribution of respiratory mucin proteins in human nasal mucosa. Laryngoscope,2003:113:520-524.
11Jung HH, Lee JH, Kim YT. et al.. Expression of mucin genes in chronic et hmoiditis. Am J Rhinoi 2000,14:163-70
12 Maria TP, Pawandeep K, Aujla MS. Immunohistochemical analyses of muc5ac mucin expression in sinus mucosa of chi ldren wi th sinusi t is and controls. Ann otology Larynagology.2005,114(12):958-965.
13 SeongJK, K00 JA, LEE WJ. Upregulation of MUC8 and downregulation of muc5ac by inflammatory mediators in human nasal polyps and cultured nasal epi thelium. Acta Otolaryngol,2002,122:401-407
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