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| 糖尿病导致的尾加压素II及其受体的上调在TGF-β介导的肾纤维化和功能不全发挥重要作用 |
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| Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-β1-mediated renal fibrosis and dysfunction |
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| Tian L., Li C., Qi J., Fu P., Yu X., Li X., Cai L. 2009/5/29 18:38:57 |
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American Journal of Physiology - Endocrinology and Metabolism, 2008, Volume 295, Issue 5
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| Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-β1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-β-D-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10-8 mol/l UII for 48 h caused a significant increase of TGF-β1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- β1 by UII. Furthermore, exposure of NRK-52E cells to TGF-β1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-β1-mediated renal fibrosis and dysfunction. Copyright © 2008 the American Physiological Society. |
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| Correspondence Address: Li, C.; Dept. of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin Univ., Changchun, China; email: lic@jlu.edu.cn |
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 疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。
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