特应性皮炎小鼠模型皮损中miR-223和TSLP的表达及分析
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摘要
目的通过测定miR-223和TSLP在MC903诱导特应性皮炎小鼠模型皮损中的表达,分析两者在特应性皮炎发病中的相关性,阐明miR-223在特应性皮炎发病过程中的作用及其与TSLP的关系。方法建立MC903诱导的特应性皮炎小鼠模型,检测模型皮损中miR-223和TSLP的相对表达量,进一步在miR-223基因敲除鼠中分析TSLP的表达变化及疾病严重程度的改变。结果在WT鼠中,经MC903诱导的模型组较对照组皮损中miR-223和TSLP表达均明显上调,但在miR-223-/-鼠模型组皮损中miR-223和TSLP表达均下调,且特应性皮炎炎症反应减轻。结论 miR-223加重特应性皮炎的炎症反应,miR-223可能通过调节TSLP的表达参与小鼠特应性皮炎的发病过程。
Objective To detect the expressions of miR-223 and TSLP in skin lesions of MC903-induced mice model with atopic dermatitis,to analyze their correlation in the pathogenesis of atopic dermatitis and to elucidate the role of miR-223 in the pathogenesis of atopic dermatitis and its relationship with TSLP. Methods The mice model of atopic dermatitis induced by MC903 was established,and the relative expression levels of miR-223 and TSLP in the model skin lesions were detected. Furthermore,the changes in TSLP expression level and the severity of AD were analyzed in miR-223 knockout mice. Results Compared with the control group of C57 BL/6 J mice,the expressions of miR-223 and TSLP were significantly up-regulated in the skin lesions of the model group in C57 BL/6 J mice. However,the expressions of miR-223 and TSLP were down-regulated in the skin lesions of the model group in miR-223-/-mice,and the inflammatory response of atopic dermatitis was alleviated in the model group of miR-223-/-mice. Conclusion miR-223 aggravates the in-flammatory response in atopic dermatitis,so that miR-223 may be involved in the pathogenesis of atopic dermatitis in mice by regulating TSLP expression.
Objective To detect the expressions of miR-223 and TSLP in skin lesions of MC903-induced mice model with atopic dermatitis,to analyze their correlation in the pathogenesis of atopic dermatitis and to elucidate the role of miR-223 in the pathogenesis of atopic dermatitis and its relationship with TSLP. Methods The mice model of atopic dermatitis induced by MC903 was established,and the relative expression levels of miR-223 and TSLP in the model skin lesions were detected. Furthermore,the changes in TSLP expression level and the severity of AD were analyzed in miR-223 knockout mice. Results Compared with the control group of C57 BL/6 J mice,the expressions of miR-223 and TSLP were significantly up-regulated in the skin lesions of the model group in C57 BL/6 J mice. However,the expressions of miR-223 and TSLP were down-regulated in the skin lesions of the model group in miR-223-/-mice,and the inflammatory response of atopic dermatitis was alleviated in the model group of miR-223-/-mice. Conclusion miR-223 aggravates the in-flammatory response in atopic dermatitis,so that miR-223 may be involved in the pathogenesis of atopic dermatitis in mice by regulating TSLP expression.
引文
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[25]Wang JF,Yu ML,Yu G,et al.Serum miR-146a and miR-223 as potential new biomarkers for sepsis[J].Biochem Biophys Res Commun,2010,394(1):184-188.
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[2]Spergel JM.Epidemiology of atopic dermatitis and atopic march in children[J].Immunol Allergy Clin North Am,2010,30(3):269-280.
[3]赵巍,刘俊峰,陈达灿,等.半抗原诱导特应性皮炎小鼠模型的研究进展[J].中国皮肤性病学杂志,2015,29(8):855-857.
[4]Mack GS.MicroRNA gets down to business[J].Nat Biotechnol,2007,25(6):631-638.
[5]Lu TX,Rothenberg ME.Diagnostic,functional,and therapeutic roles of microRNA in allergic diseases[J].J Allergy Clin Immunol,2013,132(1):3-13.
[6]王奕,王克玉.复杂皮肤病的microRNAs相关性研究进展[J].中国皮肤性病学杂志,2016,28(11):1168-1171.
[7]Sonkoly E,Janson P,Majuri ML,et al.MiR-155 is overexpressed in patients with atopic dermatitis and modulates Tcell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4[J].J Allergy Clin Immunol,2010,126(3):581-589.
[8]Vennegaard MT,Bonefeld CM,Hagedorn PH,et al.Allergic contact dermatitis induces upregulation of identical microRNAs in humans and mice[J].Contact Dermatitis,2012,67(5):298-305.
[9]王璨,王晓钰,于曦等.卡泊三醇诱导小鼠特应性皮炎模型的最适条件探索[J].中国药理学通报,2016,32(7):1027-1032.
[10]Zhang Z,Hener P,Frossard N,et al.Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma[J].Proc Natl Acad Sci U S A,2009,106(5):1536-1541.
[11]Soumelis V,Reche PA,Kanzler H,et al.Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP[J].Nat Immunol,2002,3(7):673-680.
[12]瞿旻晔,袁晓琳,马健.特应性皮炎发病过程及其机制研究现状探讨[J].中国皮肤性病学杂志,2015,29(10):1085-1087.
[13]Tatsuno K,Fujiyama T,Yamaguchi H,et al.TSLP directly interacts with skin-homing Th2 cells highly expressing its receptor to enhance IL-4 production in atopic dermatitis[J].J Invest Dermatol,2015,135(12):3017-3024.
[14]Liu YJ.Thymic stromal lymphopoietin:master switch for allergic inflammation[J].J Exp Med,2006,203(2):269-273.
[15]宫泽琨,杨雨潮,解奎霞,等.特应性皮炎患儿外周血胸腺基质淋巴细胞生成素与白介素-25的表达及相关性[J].中国皮肤性病学杂志,2016,30(1):17-19.
[16]Liu TY,Chen SU,Kuo SH,et al.E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223:possible correlation with stage and treatment response[J].Mod Pathol,2010,23(11):1507-1517.
[17]Laios A,O'Toole S,Flavin R,et al.Potential role of miR-9 and miR-223 in recurrent ovarian cancer[J].Mol Cancer,2008,7:35-72.
[18]Wong QW,Lung RW,Law PT,et al.MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1[J].Gastroenterology,2008,135(1):257-269.
[19]Eyholzer M,Schmid S,Schardt JA,et al.Complexity of miR-223 regulation by CEBPA in human AML[J].Leuk Res,2010,34(5):672-676.
[20]Johnnidis JB,Harris MH,Wheeler RT,et al.Regulation of progenitor cell proliferation and granulocyte function by microRNA-223[J].Nature,2008,451(7182):1125-1129.
[21]Fazi F,Racanicchi S,Zardo G,et al.Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein[J].Cancer Cell,2007,12(5):457-466.
[22]Yuan JY,Wang F,Yu J,et al.MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells[J].J Cell Mol Med,2009,13(11-12):4551-4559.
[23]Wang H,Chao K,Ng SC,et al.Pro-inflammatory miR-223mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease[J].Genome Biol,2016,17:58-72.
[24]Fulci V,Scappucci G,Sebastiani GD,et al.miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis[J].Hum Immunol,2010,71(2):206-211.
[25]Wang JF,Yu ML,Yu G,et al.Serum miR-146a and miR-223 as potential new biomarkers for sepsis[J].Biochem Biophys Res Commun,2010,394(1):184-188.
[26]Lu Han,Buchan Rachel,Cook Stuart.MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism[J].Cardiovasc Res,2010,86(3):410-420.
[27]Yu CH,Xu CF,Li YM.Association of MicroRNA-223 expression with hepatic ischemia/reperfusion injury in mice[J].Dig Dis Sci,2009,54(11):2362-2366.