STC-1在新生奶牛肾脏和十二指肠中的表达和定位研究
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摘要
斯钙素-1(STC-1)是一种最早在硬骨鱼特有的斯坦尼氏小体发现的多肽类激素,后来在人和多种哺乳动物体内也发现STC-1的基因表达并有一些蛋白定位的报道。STC-1参与钙磷代谢,抑制钙的吸收和促进磷酸盐的吸收、重吸收,抑制磷酸盐的排泄。在分子和组织水平探索STC-1在奶牛体内的表达,对研究奶牛钙磷代谢的机理具有重要的意义,同时为探索防治奶牛钙磷代谢病提供新的思路。
为从基因水平检测在中华荷斯坦奶牛肾脏和十二指肠中是否有STC-1基因的表达,本试验选择1日龄中华荷斯坦犊牛,通过提取试验奶牛肾脏和十二指肠组织的总RNA,建立PCR反应体系,克隆STC-1 cDNA的部分序列。结果显示,STC-1基因在中华荷斯坦奶牛肾脏和十二指肠组织中有表达。将所克隆的STC-1 cDNA序列连接T载体、转化、测序。同源分析显示与Bos taurus的STC-1基因相应序列的核苷酸序列同源性达到100%。
在钙磷代谢过程中,十二指肠是钙和磷的最重要的吸收部位,而肾脏是重要的重吸收和排泄的器官。为探索STC-1蛋白在奶牛钙磷代谢中的生理作用,本试验运用免疫组化技术对STC-1蛋白在1日龄中华荷斯坦犊牛肾脏和十二指肠的分布进行检测,结果显示在肾脏的近曲小管和远曲小管上皮细胞有明显的棕黄色阳性染色,主要集中在上皮细胞的胞浆内,十二指肠的肠腺和杯状细胞也呈现出明显的棕黄色；运用原位杂交技术对STC-1 mRNA在肾脏和十二指肠进行检测,结果显示在奶牛肾脏的近端小管和皮质升支粗段有明显的杂交信号,在远端小管有微弱的杂交信号。在肾小球区域则见不到棕黄色的染色。在十二指肠的杯状细胞边缘和肠腺有明显的杂交信号。
本实验首次证实了中华荷斯坦奶牛肾脏和十二指肠中有STC-1基因的表达,首次在中华荷斯坦奶牛肾脏和十二指肠组织中进行了STC-1蛋白和mRNA的定位研究。本试验为进一步研究STC-1的基因结构、在不同组织中的表达及表达模式提供了新的材料,并为研究STC-1的生理作用、探索预防和治疗奶牛钙磷代谢病提供新的资料。
Stanniocalcin-1 (STC-1) is a peptide hormones that was firstly idendified in the bony fish specific corpuscle of stannius(CS). Later, it was reported that STC gene express in human and a variety of mammals and had some protein and mRNA distribution reports. STC-1 participates in calcium and phosphorus metabolism. STC-1 inhibits the absorption of calcium, promotes the absorption of phosphate, inhibits the excretion of phosphate. The structure and function of muscle and blood vessel formation and reproductive process were also affected by STC-1. In dairy cows, exploring STC-1 expression in the horizontal of molecular and tissue level is significant to study the mechanism of calcium and phosphorus metabolism. On the other hand, it may provide a new way to explore prevention and control of calcium and phosphorus metabolism disease.
To test STC-1 expression or not, and distribution in kidney and duodenum of Chinese Holstein cows from the gene level, the total RNA of kidney and duodenum of experimenting one day old dairy cows was extracted, the purpose cDNA was synthesized through the established PCR reaction system. The result showed that, STC-1 gene expressed in kidney and duodenal of the Chinese Holstein cows. The cloned purpose cDNA was connected to T vector, and was transformed and sequenced. Sequence analysis showed that, the partial sequence of STC-1 gene nucleotide sequence homology is 100% corresponding with Bos taurus.
In calcium and phosphorus metabolism, the duodenum was the most important calcium and phosphorus absorption site, and kidney was important organ of re-absorption and excretion. To explore the physiological role of STC-1 protein in diary cow's calcium and phosphorus metabolism, STC-1 protein was tested in the kidney and duodenum of one day old Chinese Holstein cows. The results of immunohistochemistry showed that the epithelial cells of kidney proximal tubule and distal tubule have significant brown staining, mainly in the cytoplasm of epithelial cells. And glands and duodenal goblet cells of the intestinal showed clear brown staining. STC-1 mRNA was tested in the kidney and duodenum by in situ hybridization. The results showed that, the epithelial cells in kidney proximal tubule, cortical thick ascending limb have conspicuous hybridization signals, and with weak hybridization signals in the distal tubule. And no positive brown staining was showed in the glomerular regions. In the duodenum, it is significant hybridization signal in the edge of goblet cells and intestinal glands.
In this experiment, it was the first time prove that STC-1 gene expressed in kidney and duodenum of the Chinese Holstein cows, and also was the first localization of STC-1 protein and mRNA in the kidney and duodenal tissues of Chinese Holstein cows. The results provided new materials for further studying of STC-1 gene structure, expression in different tissues and expression patterns, created the conditions for researching the physiological role of STC-1, and provided new informations for exploring prevention and treatments of calcium and phosphorus metabolic diseases of dairy cows.
为从基因水平检测在中华荷斯坦奶牛肾脏和十二指肠中是否有STC-1基因的表达,本试验选择1日龄中华荷斯坦犊牛,通过提取试验奶牛肾脏和十二指肠组织的总RNA,建立PCR反应体系,克隆STC-1 cDNA的部分序列。结果显示,STC-1基因在中华荷斯坦奶牛肾脏和十二指肠组织中有表达。将所克隆的STC-1 cDNA序列连接T载体、转化、测序。同源分析显示与Bos taurus的STC-1基因相应序列的核苷酸序列同源性达到100%。
在钙磷代谢过程中,十二指肠是钙和磷的最重要的吸收部位,而肾脏是重要的重吸收和排泄的器官。为探索STC-1蛋白在奶牛钙磷代谢中的生理作用,本试验运用免疫组化技术对STC-1蛋白在1日龄中华荷斯坦犊牛肾脏和十二指肠的分布进行检测,结果显示在肾脏的近曲小管和远曲小管上皮细胞有明显的棕黄色阳性染色,主要集中在上皮细胞的胞浆内,十二指肠的肠腺和杯状细胞也呈现出明显的棕黄色；运用原位杂交技术对STC-1 mRNA在肾脏和十二指肠进行检测,结果显示在奶牛肾脏的近端小管和皮质升支粗段有明显的杂交信号,在远端小管有微弱的杂交信号。在肾小球区域则见不到棕黄色的染色。在十二指肠的杯状细胞边缘和肠腺有明显的杂交信号。
本实验首次证实了中华荷斯坦奶牛肾脏和十二指肠中有STC-1基因的表达,首次在中华荷斯坦奶牛肾脏和十二指肠组织中进行了STC-1蛋白和mRNA的定位研究。本试验为进一步研究STC-1的基因结构、在不同组织中的表达及表达模式提供了新的材料,并为研究STC-1的生理作用、探索预防和治疗奶牛钙磷代谢病提供新的资料。
Stanniocalcin-1 (STC-1) is a peptide hormones that was firstly idendified in the bony fish specific corpuscle of stannius(CS). Later, it was reported that STC gene express in human and a variety of mammals and had some protein and mRNA distribution reports. STC-1 participates in calcium and phosphorus metabolism. STC-1 inhibits the absorption of calcium, promotes the absorption of phosphate, inhibits the excretion of phosphate. The structure and function of muscle and blood vessel formation and reproductive process were also affected by STC-1. In dairy cows, exploring STC-1 expression in the horizontal of molecular and tissue level is significant to study the mechanism of calcium and phosphorus metabolism. On the other hand, it may provide a new way to explore prevention and control of calcium and phosphorus metabolism disease.
To test STC-1 expression or not, and distribution in kidney and duodenum of Chinese Holstein cows from the gene level, the total RNA of kidney and duodenum of experimenting one day old dairy cows was extracted, the purpose cDNA was synthesized through the established PCR reaction system. The result showed that, STC-1 gene expressed in kidney and duodenal of the Chinese Holstein cows. The cloned purpose cDNA was connected to T vector, and was transformed and sequenced. Sequence analysis showed that, the partial sequence of STC-1 gene nucleotide sequence homology is 100% corresponding with Bos taurus.
In calcium and phosphorus metabolism, the duodenum was the most important calcium and phosphorus absorption site, and kidney was important organ of re-absorption and excretion. To explore the physiological role of STC-1 protein in diary cow's calcium and phosphorus metabolism, STC-1 protein was tested in the kidney and duodenum of one day old Chinese Holstein cows. The results of immunohistochemistry showed that the epithelial cells of kidney proximal tubule and distal tubule have significant brown staining, mainly in the cytoplasm of epithelial cells. And glands and duodenal goblet cells of the intestinal showed clear brown staining. STC-1 mRNA was tested in the kidney and duodenum by in situ hybridization. The results showed that, the epithelial cells in kidney proximal tubule, cortical thick ascending limb have conspicuous hybridization signals, and with weak hybridization signals in the distal tubule. And no positive brown staining was showed in the glomerular regions. In the duodenum, it is significant hybridization signal in the edge of goblet cells and intestinal glands.
In this experiment, it was the first time prove that STC-1 gene expressed in kidney and duodenum of the Chinese Holstein cows, and also was the first localization of STC-1 protein and mRNA in the kidney and duodenal tissues of Chinese Holstein cows. The results provided new materials for further studying of STC-1 gene structure, expression in different tissues and expression patterns, created the conditions for researching the physiological role of STC-1, and provided new informations for exploring prevention and treatments of calcium and phosphorus metabolic diseases of dairy cows.
引文
1. 蔡文琴主编.组织化学与细胞化学.北京：人民卫生出版社,2009
2.陈维娜,朱广瑾.斯钙素的研究进展.生理科学进展,2008,39(3)：225-228
3.黄培林,吴平平,陈宝安,等.大肠癌患者外周血人类斯钙素基因的检测及其意义.中华消化杂志,2005,25(5)：259-261
4. 冯清林,姜蓉,雷波,等.2种苏木精染液在免疫组织化学中复染效果的比较.2010,35(11)：1700-1701
5.冯永利,李兵,杨朝宽,等.犬冠状静脉窦阻塞后心肌肌钙蛋白Ⅰ和纤维连接蛋白免疫组织化学的研究.中华老年心脑血管病杂志,2011,13(2)：157-161
6.李宾,王坤英,李卫国,等.中华大蟾蜍斯钙素基因的组织表达及其在肾脏中的细胞定位.动物学报,2008,54(4)：712-718
7. 李卫国,罗艳蕊,王坤英,等. 斯钙素与哺乳动物生殖的研究进展生理科学进展,2003,34(3)：275-277
8.李卫国,李金亭,高春建.人和哺乳动物斯钙素研究概况.生理科学进展,2000,31(1)：79-81
9.卢慎.应用免疫组化、原位杂交及间接原位PCR诊断弓形虫淋巴结炎.中国实验诊断学.2008,12(10)：1305-1307
10.邱曙东,宋天保主编.组织化学与免疫组织化学.北京：科学出版社,2008
11.唐小龙,张洹.人类斯钙素1的生物学特性研究进展.中国病理生理杂志,2008,24(3)：617-621
12.腾可导主编.彩图家畜组织学与胚胎学实验指导.北京：中国农业大学出版社,2008
13.邢传平,刘斌,李宁,等.泡状棘球蚴病16例临床病理学及免疫组化观察.西北国防医学杂志,2005,26(5)：353-356
14.徐美荣,韦成益,单国平,等.外周血人类斯钙素1基因表达与乳腺癌微转移的关系.肿瘤.2007,27(12)：977-980
15.杨丰利,李小杉,何宝祥.奶牛斯钙素-1研究进展.中国兽医杂志,2010,46(5)：54-56
16.姚荣荣.消化道组织学与免疫组织化学的研究.[硕士学位论文].武汉：华中农业大学图书馆,2008
17.张伟,彭大云,陈晓东,等.乳腺癌HER2基因荧光原位杂交与显色原位杂交检测对比研究.华南国防医学杂志.2011,25(1)：13-16
18.张延涛,王静蓉.人类斯钙素生物学特性的相关研究.医学综述,2009,15(19)：2926-2928
19. Chang A C, Cha J, Koentgen F, et al. Themurine stanniocalcin 1 gene is not essential for growth and development. Mol Cel Biol,2005,25(23):10604-10610
20. Chang A C, Jelinek D A,Reddel R R. Mammalian stanniocalcins and cancer. Endocr Relat Cancer,2003,10(3):359-373
21. Chang ACM, Jeffrey K J, Tokutake Y, et al.Human stanniocalcin (STC):genomic structure, chromosomal localization, and the presence of CAG trinucleotide repeats. Genomics,1998,47:393-398
22. Chang ACM and Reddel R R. Identification of a second stanniocalcin cDNA in mouse and human:stanniocalcin 2. Mol Cell Endocrinol,1998,141:95-99
23. Chang ACM, Janosi J, Hulsbeek M, et al. A novel human cDNA highly homologous to the fish hormone stanniocalcin. Mol Cell Endocrinol,1995,112:241-247
24. Charpentier A H,Bednarek A K,Daniel R L,et al.Effects of estrogen on global gene expression:identification of novel targets of estrogen action. Cancer Resercher,2002,62(93):5977-5983
25. Deol H K, Varghese R, Wagner G F, et al. Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation. Endocrinology,2000,141: 3412-3421
26. DiMattia G E, Varghese R,and Wagner GF. Molecular cloning and characterization of stanniocalcin-related protein. Mol Cell Endocrinol,1998,146:137-140
27. Eisenhofer G, Huynh T T, Pacak K, et al. Distinct gene expression profiles in norepinephrine and epinephrine producing hereditary and sporadic pheochromocytomas:activation of hypoxia driven angiogenic pathways in yon Hippel-Lindau syndrome. Endocr Relat Cancer,2004,1(4):897-911
28. Filvaroff E H, Guillet S, Zlot C, et al. Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice. Endocrinology,2002,143(9):3681-3690
29. Franzen A M, Zhang K Z, Westberg J A, et al. Expression of stanniocalcin in the epithelium of human choroid plexus. Brain Research,2000,887:440-443
30. Fujiwara Y, Sugita Y, Nakamori S, et al. Assessment of stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. Int J Oncol,2000, 16:799-804
31. Hasilo C P, McCudden C R, Gillespie J R, et al. Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation. Am J Physiol, 2005,289(4):E634-E642
32. Ishibashi K, Miyamoto K, Taketani Y, et al. Molecular cloning of a second human stanniocalcin homologue (STC2). Biochem Biophys Res Commun,1998,250:252-258
33. James K, Seitelbach M, McCudden C R, et al. Evidence for stanniocalcin binding activity in mammalian blood and glomerular filtrate. Kidney Int,2005,67(2): 477-482
34. Jiang W Q, Chang A C, Satoh M, et al. The distribution of stanniocalcin 1 protein in fetal mouse tissues suggests a role in bone and muscle development. J Endocrinol, 2000,165:457-466
35. Koide Y, Sasaki T. Stanniocalcin-1(STC-1)as a molecular marker for human cancer. Rinsho Byori,2006,54(3):213-220
36. Lafeber F J and Perry S F. Experimental hypercalcemia induces hypocalcin release and inhibits branchial Ca2+ influx in freshwater trout. Gen Comp Endocr,1988,72: 136-143
37. Lu M, Wagner G F,and Renfro J L. Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture. Am J Patho,1994,267:R1356-R1362
38. Luo C W, Kawamura K, Klein C, et al. Paracrine regulation of ovarian granulosa cell diferentiation by stanniocalcin(STC)1:mediation throngh specific STC1 receptors Mol Endocfinol,2004,18(8):2085-2096
39. Madsen K L, Tavernini M M, Yachimec C, et al. Stanniocalcin:a novel protein regulating calcium and phosphate transport acrossmammalian intestine, Am. J. Physiol.1998,274:G96-102
40. McCudden C R, Majewski A, Chakrabarti S, et al. Colocalization of stanniocalcin-1 ligand and receptor in human breast carcinomas. Mol Cel Endocfinol,2004,213(2): 167-172
41. McCudden C R, James K A, Hasilo C, et al. Characterization of mammalian stanniocalcin receptors:mitochondrial targeting of ligand and receptor for regulation of cellular metabolism. J Biol Chem,2002,277(47):45249-45258
42. Miura W, Mizunashi K, Kimura N, et al. Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines. APMIS,2000,108:367-372
43. Moore E E, Kuestner R E, Conklin DC, et al. Stanniocalcin 2:characterization of the protein and its localization to human pancreatic alpha cells. Hormone and Metabolism Research,1999,31:406-414
44. Niu P D, Radman D P,Jworski E M, et al.Demelopment of a human stanniocalcin radioimmunoassay:serum and tissue hormone levels and pharmacokinetics in the rat,Mol Cell Endocrinol.2000,162:131-144
45. Niu P D, Olsen H S, Gents R, et al. Immunolocalization of stanniocalcin in human kidney. Mol Cell Endocrinol,1998,137:155-159
46. Olsen H S, Cepeda M A, Zhang Q Q, et al. Human stanniocalcin:a possible hormonal regulator of mineral metabolism. PNAS,1996,93:1792-1796
47. Paciga M, James K, Gillespie J R, et al. Evidence for crosstalk between stanniocalcins. Can J Physiol Pharmacol,2005,83(11):953-956
48. Reddy P S and Housman D E. The complex pathology of trinucleotide repeats. Curr Opin CellBiol,1997,9:364-372
49. Rika K, Yoshiko N, Yoshie S, et al. Expression of stanniocalcin-1 in gastrointestinal tracts of neonatal and mature rats. Biochem Biophys Res Commu.,2009,389: 478-483
50. Sato N, Kokame K, Shimokado K, et al. Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells:12 up-regulated distinct genes including 5 cell growth-related,3 thrombosis-related, and 4 others. J Bioche,1998, 123:1119-1126
51. Seflachius M, Andersson L C. Upregulated expression of stanniocalcin-1 during adipogenesis. Exp Cell Res,2004,296(2):256-264
52. Sheikh H D, Bick R, Wu G Y, et al. Stanniocalcin-1 is a naturally occurring L-channel inhibitor in cardiomyocytes:relevance to human heart failure. Am J Physiol,2003,285(1):H442-H448
53. Snell R G, MacMillan J C, Cheadle J P, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat Genet,1993, 4:393-397
54. Stasko S E and Wagner G F. Stanniocalcin gene expression during mouse urogenital development:a possible role in mesenchymal-epithelial signalling. Dev Dyn,2001b, 220:49-59
55. Sundell K, Bjornsson B T, Itoh H, et al. Chum salmon(Oncorhynchus keta) stanniocalcin inhibits in vitro calcium uptake in Atlantic cod (Gadus morhua). J Comp Physiol,1992,162:489-495
56. Takagi Y, Nakamura Y, and Yamada J. Effects of the removal of the corpuscles of Stannius on the transport of calcium across the intestine of rainbow trout. Zoological Sciences,1985,2:523-530
57. Tohmiya Y, Koide Y, Fujimaki S, et al. Stanniocalcin-1 as a novel marker to detect minimal residual disease of human leukemia. Tohoku J Exp Med,2004,204(2):125-133
58. Varghese R, Wong CKC, Deol H, et al.Comparative analysis of mammalian stanniocalcin genes. Endocrinology,1998,139:4714-4725
59. Wagner G F, Fenwick J C, Park C M, et al. Comparative biochemistry and physiology of teleocalcin from sockeye and coho salmon. Gen Comp Endocr,1988,72:237-246
60. Wagner G F, Guiraudon C C, Milliken C, et al. Immunological and biological evidence for a stanniocalcin-like hormone in human kidney. PNAS,1995,92:1871-1875
61. Wong C K, Yeung H Y, Mak N K, et al. Efects of dibutyryl cAMP on stanniocalcin and stanniocalcin-related protein mRNA expression in neuroblastoma cels. J Endocrinol,2002,173(1):199-209
62. Worthington R A, Brown L, Jellinek D, et al. Expression and localisation of stanniocalcin 1 in rat bladder, kidney and ovary. Electrophoresis,1999,20:2071-2076
63. Wong C K, Ho M A, and Wagner GF. The co-localization of stanniocalcin protein, mRNA and kidney cell markers in the rat kidney. Endocrinology,1998,158:183-189
64. Wu S, Yoshiko Y, De L F. Stanniocalcin 1 acts as aparacrine regulator of growth plate chondrogenesis. J Biol Chem,2006,281(8):5120-5127
65. Yahata K, Mori K, Mukoyama M, et al. Regulation of stanniocalcin 1 and 2 expression in the kidney by klotho gene. Biochem Biophys Res Commun,2003, 310(1):128-130
66. Yeung H Y, Lai K P, Chan H Y, et al. Hypoxia-inducible factor-1-mediated activation of stan niocalcin-1 in human cancer cels. Endocrinology,2005,146(11):4951-4960
67. Yoshiko Y, Aubin J E. Stanniocalcin 1 as a pleiotropic factor in mammals. Peptides, 2004,25(10):1663-1669
68. Yoshiko Y,Aubin J E, and Maeda N.Stanniocalcin 1 (STC1) Protein and mRNA Are Developmentally Regulated During Embryonic Mouse Osteogenesis:the Potential of STC1 as an Autocrine/Paracrine Factor for Osteoblast Development and Bone Formation. Histochem Cytochem,2002,50(4):483-491
69. Yoshiko Y, Son A, Maeda S, et al. Evidence for stanniocalcin gene expression in mammalian bone. Endocrinology,1999,140:1869-1874
70. Yoshiko Y and Maeda N. In situ hybridization analysis of stanniocalcin mRNA expressing cells in the mouse kidney. Mol Cell Endocrinol,1998,141:37-40
71. Zhang K Z, Westberg J A, Paetau A, et al. High expression of stanniocalcin in differentiated brain neurons. Am J Pathol,1998,153:439-445
72. Zlot C, Ingle G, Hongo J, et al. Stanniocalcin 1 is an autocrine modulator of endothelial angiogenic responses to hepatocyte growth factor. J Biol Chem,2003, 278(48):47654-47659
2.陈维娜,朱广瑾.斯钙素的研究进展.生理科学进展,2008,39(3)：225-228
3.黄培林,吴平平,陈宝安,等.大肠癌患者外周血人类斯钙素基因的检测及其意义.中华消化杂志,2005,25(5)：259-261
4. 冯清林,姜蓉,雷波,等.2种苏木精染液在免疫组织化学中复染效果的比较.2010,35(11)：1700-1701
5.冯永利,李兵,杨朝宽,等.犬冠状静脉窦阻塞后心肌肌钙蛋白Ⅰ和纤维连接蛋白免疫组织化学的研究.中华老年心脑血管病杂志,2011,13(2)：157-161
6.李宾,王坤英,李卫国,等.中华大蟾蜍斯钙素基因的组织表达及其在肾脏中的细胞定位.动物学报,2008,54(4)：712-718
7. 李卫国,罗艳蕊,王坤英,等. 斯钙素与哺乳动物生殖的研究进展生理科学进展,2003,34(3)：275-277
8.李卫国,李金亭,高春建.人和哺乳动物斯钙素研究概况.生理科学进展,2000,31(1)：79-81
9.卢慎.应用免疫组化、原位杂交及间接原位PCR诊断弓形虫淋巴结炎.中国实验诊断学.2008,12(10)：1305-1307
10.邱曙东,宋天保主编.组织化学与免疫组织化学.北京：科学出版社,2008
11.唐小龙,张洹.人类斯钙素1的生物学特性研究进展.中国病理生理杂志,2008,24(3)：617-621
12.腾可导主编.彩图家畜组织学与胚胎学实验指导.北京：中国农业大学出版社,2008
13.邢传平,刘斌,李宁,等.泡状棘球蚴病16例临床病理学及免疫组化观察.西北国防医学杂志,2005,26(5)：353-356
14.徐美荣,韦成益,单国平,等.外周血人类斯钙素1基因表达与乳腺癌微转移的关系.肿瘤.2007,27(12)：977-980
15.杨丰利,李小杉,何宝祥.奶牛斯钙素-1研究进展.中国兽医杂志,2010,46(5)：54-56
16.姚荣荣.消化道组织学与免疫组织化学的研究.[硕士学位论文].武汉：华中农业大学图书馆,2008
17.张伟,彭大云,陈晓东,等.乳腺癌HER2基因荧光原位杂交与显色原位杂交检测对比研究.华南国防医学杂志.2011,25(1)：13-16
18.张延涛,王静蓉.人类斯钙素生物学特性的相关研究.医学综述,2009,15(19)：2926-2928
19. Chang A C, Cha J, Koentgen F, et al. Themurine stanniocalcin 1 gene is not essential for growth and development. Mol Cel Biol,2005,25(23):10604-10610
20. Chang A C, Jelinek D A,Reddel R R. Mammalian stanniocalcins and cancer. Endocr Relat Cancer,2003,10(3):359-373
21. Chang ACM, Jeffrey K J, Tokutake Y, et al.Human stanniocalcin (STC):genomic structure, chromosomal localization, and the presence of CAG trinucleotide repeats. Genomics,1998,47:393-398
22. Chang ACM and Reddel R R. Identification of a second stanniocalcin cDNA in mouse and human:stanniocalcin 2. Mol Cell Endocrinol,1998,141:95-99
23. Chang ACM, Janosi J, Hulsbeek M, et al. A novel human cDNA highly homologous to the fish hormone stanniocalcin. Mol Cell Endocrinol,1995,112:241-247
24. Charpentier A H,Bednarek A K,Daniel R L,et al.Effects of estrogen on global gene expression:identification of novel targets of estrogen action. Cancer Resercher,2002,62(93):5977-5983
25. Deol H K, Varghese R, Wagner G F, et al. Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation. Endocrinology,2000,141: 3412-3421
26. DiMattia G E, Varghese R,and Wagner GF. Molecular cloning and characterization of stanniocalcin-related protein. Mol Cell Endocrinol,1998,146:137-140
27. Eisenhofer G, Huynh T T, Pacak K, et al. Distinct gene expression profiles in norepinephrine and epinephrine producing hereditary and sporadic pheochromocytomas:activation of hypoxia driven angiogenic pathways in yon Hippel-Lindau syndrome. Endocr Relat Cancer,2004,1(4):897-911
28. Filvaroff E H, Guillet S, Zlot C, et al. Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice. Endocrinology,2002,143(9):3681-3690
29. Franzen A M, Zhang K Z, Westberg J A, et al. Expression of stanniocalcin in the epithelium of human choroid plexus. Brain Research,2000,887:440-443
30. Fujiwara Y, Sugita Y, Nakamori S, et al. Assessment of stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. Int J Oncol,2000, 16:799-804
31. Hasilo C P, McCudden C R, Gillespie J R, et al. Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation. Am J Physiol, 2005,289(4):E634-E642
32. Ishibashi K, Miyamoto K, Taketani Y, et al. Molecular cloning of a second human stanniocalcin homologue (STC2). Biochem Biophys Res Commun,1998,250:252-258
33. James K, Seitelbach M, McCudden C R, et al. Evidence for stanniocalcin binding activity in mammalian blood and glomerular filtrate. Kidney Int,2005,67(2): 477-482
34. Jiang W Q, Chang A C, Satoh M, et al. The distribution of stanniocalcin 1 protein in fetal mouse tissues suggests a role in bone and muscle development. J Endocrinol, 2000,165:457-466
35. Koide Y, Sasaki T. Stanniocalcin-1(STC-1)as a molecular marker for human cancer. Rinsho Byori,2006,54(3):213-220
36. Lafeber F J and Perry S F. Experimental hypercalcemia induces hypocalcin release and inhibits branchial Ca2+ influx in freshwater trout. Gen Comp Endocr,1988,72: 136-143
37. Lu M, Wagner G F,and Renfro J L. Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture. Am J Patho,1994,267:R1356-R1362
38. Luo C W, Kawamura K, Klein C, et al. Paracrine regulation of ovarian granulosa cell diferentiation by stanniocalcin(STC)1:mediation throngh specific STC1 receptors Mol Endocfinol,2004,18(8):2085-2096
39. Madsen K L, Tavernini M M, Yachimec C, et al. Stanniocalcin:a novel protein regulating calcium and phosphate transport acrossmammalian intestine, Am. J. Physiol.1998,274:G96-102
40. McCudden C R, Majewski A, Chakrabarti S, et al. Colocalization of stanniocalcin-1 ligand and receptor in human breast carcinomas. Mol Cel Endocfinol,2004,213(2): 167-172
41. McCudden C R, James K A, Hasilo C, et al. Characterization of mammalian stanniocalcin receptors:mitochondrial targeting of ligand and receptor for regulation of cellular metabolism. J Biol Chem,2002,277(47):45249-45258
42. Miura W, Mizunashi K, Kimura N, et al. Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines. APMIS,2000,108:367-372
43. Moore E E, Kuestner R E, Conklin DC, et al. Stanniocalcin 2:characterization of the protein and its localization to human pancreatic alpha cells. Hormone and Metabolism Research,1999,31:406-414
44. Niu P D, Radman D P,Jworski E M, et al.Demelopment of a human stanniocalcin radioimmunoassay:serum and tissue hormone levels and pharmacokinetics in the rat,Mol Cell Endocrinol.2000,162:131-144
45. Niu P D, Olsen H S, Gents R, et al. Immunolocalization of stanniocalcin in human kidney. Mol Cell Endocrinol,1998,137:155-159
46. Olsen H S, Cepeda M A, Zhang Q Q, et al. Human stanniocalcin:a possible hormonal regulator of mineral metabolism. PNAS,1996,93:1792-1796
47. Paciga M, James K, Gillespie J R, et al. Evidence for crosstalk between stanniocalcins. Can J Physiol Pharmacol,2005,83(11):953-956
48. Reddy P S and Housman D E. The complex pathology of trinucleotide repeats. Curr Opin CellBiol,1997,9:364-372
49. Rika K, Yoshiko N, Yoshie S, et al. Expression of stanniocalcin-1 in gastrointestinal tracts of neonatal and mature rats. Biochem Biophys Res Commu.,2009,389: 478-483
50. Sato N, Kokame K, Shimokado K, et al. Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells:12 up-regulated distinct genes including 5 cell growth-related,3 thrombosis-related, and 4 others. J Bioche,1998, 123:1119-1126
51. Seflachius M, Andersson L C. Upregulated expression of stanniocalcin-1 during adipogenesis. Exp Cell Res,2004,296(2):256-264
52. Sheikh H D, Bick R, Wu G Y, et al. Stanniocalcin-1 is a naturally occurring L-channel inhibitor in cardiomyocytes:relevance to human heart failure. Am J Physiol,2003,285(1):H442-H448
53. Snell R G, MacMillan J C, Cheadle J P, et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat Genet,1993, 4:393-397
54. Stasko S E and Wagner G F. Stanniocalcin gene expression during mouse urogenital development:a possible role in mesenchymal-epithelial signalling. Dev Dyn,2001b, 220:49-59
55. Sundell K, Bjornsson B T, Itoh H, et al. Chum salmon(Oncorhynchus keta) stanniocalcin inhibits in vitro calcium uptake in Atlantic cod (Gadus morhua). J Comp Physiol,1992,162:489-495
56. Takagi Y, Nakamura Y, and Yamada J. Effects of the removal of the corpuscles of Stannius on the transport of calcium across the intestine of rainbow trout. Zoological Sciences,1985,2:523-530
57. Tohmiya Y, Koide Y, Fujimaki S, et al. Stanniocalcin-1 as a novel marker to detect minimal residual disease of human leukemia. Tohoku J Exp Med,2004,204(2):125-133
58. Varghese R, Wong CKC, Deol H, et al.Comparative analysis of mammalian stanniocalcin genes. Endocrinology,1998,139:4714-4725
59. Wagner G F, Fenwick J C, Park C M, et al. Comparative biochemistry and physiology of teleocalcin from sockeye and coho salmon. Gen Comp Endocr,1988,72:237-246
60. Wagner G F, Guiraudon C C, Milliken C, et al. Immunological and biological evidence for a stanniocalcin-like hormone in human kidney. PNAS,1995,92:1871-1875
61. Wong C K, Yeung H Y, Mak N K, et al. Efects of dibutyryl cAMP on stanniocalcin and stanniocalcin-related protein mRNA expression in neuroblastoma cels. J Endocrinol,2002,173(1):199-209
62. Worthington R A, Brown L, Jellinek D, et al. Expression and localisation of stanniocalcin 1 in rat bladder, kidney and ovary. Electrophoresis,1999,20:2071-2076
63. Wong C K, Ho M A, and Wagner GF. The co-localization of stanniocalcin protein, mRNA and kidney cell markers in the rat kidney. Endocrinology,1998,158:183-189
64. Wu S, Yoshiko Y, De L F. Stanniocalcin 1 acts as aparacrine regulator of growth plate chondrogenesis. J Biol Chem,2006,281(8):5120-5127
65. Yahata K, Mori K, Mukoyama M, et al. Regulation of stanniocalcin 1 and 2 expression in the kidney by klotho gene. Biochem Biophys Res Commun,2003, 310(1):128-130
66. Yeung H Y, Lai K P, Chan H Y, et al. Hypoxia-inducible factor-1-mediated activation of stan niocalcin-1 in human cancer cels. Endocrinology,2005,146(11):4951-4960
67. Yoshiko Y, Aubin J E. Stanniocalcin 1 as a pleiotropic factor in mammals. Peptides, 2004,25(10):1663-1669
68. Yoshiko Y,Aubin J E, and Maeda N.Stanniocalcin 1 (STC1) Protein and mRNA Are Developmentally Regulated During Embryonic Mouse Osteogenesis:the Potential of STC1 as an Autocrine/Paracrine Factor for Osteoblast Development and Bone Formation. Histochem Cytochem,2002,50(4):483-491
69. Yoshiko Y, Son A, Maeda S, et al. Evidence for stanniocalcin gene expression in mammalian bone. Endocrinology,1999,140:1869-1874
70. Yoshiko Y and Maeda N. In situ hybridization analysis of stanniocalcin mRNA expressing cells in the mouse kidney. Mol Cell Endocrinol,1998,141:37-40
71. Zhang K Z, Westberg J A, Paetau A, et al. High expression of stanniocalcin in differentiated brain neurons. Am J Pathol,1998,153:439-445
72. Zlot C, Ingle G, Hongo J, et al. Stanniocalcin 1 is an autocrine modulator of endothelial angiogenic responses to hepatocyte growth factor. J Biol Chem,2003, 278(48):47654-47659