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Transforming growth factor--#beta#1 and Snail1 mediate tubular epithelial--mesenchymal transition in diabetic rats

Fang Kaiyun, Lou Jinglei, Xiao Ying, Shi Mingjuan, Gui Huazhen, Guo Bing, Zhang Guozhong

Department of Pathophysiology, Guiyang Medical College.Guiyang 550004,Guizhou

Abstract

The present study was aimed to explore the expressions of transforming growth factor-#beta#1 （TGF-#beta#1） and Snail1 in renal tissues of diabetic rats, and their role in tubular epithelial-mesenchymal transition （TEMT）. Induced diabetic rats were randomly divided into 2-, 4-, 8-, 12-, 16-, 20-, 24-week and 16wA, 20wA, 24wA groups. The rats in 16wA, 20wA and 24wA groups were treated with insulin to control blood glucose to the normal level from the 13th week. The age-matched rats were set as controls. Blood glucose, 24-hour urine protein, serum creatinine （Scr）, kidney index of rats were measured. PAS staining was used to observe the renal pathological changes. Immunohistochemical staining and （or） Western blot were employed to determine the expressions of TGF-#beta#1, Snail1, E-cadherin, #alpha#-smooth muscle actin （#alpha#-SMA） and fibronectin （FN） proteins. The expressions of Snail1 and E-cadherin mRNAs in renal cortex were examined by RT-PCR. Blood glucose, 24-hour urine protein, Scr and kidney index increased remarkably in diabetic rats as compared with those in the control groups （P〈0.05, P〈0.01） and insulin-treated rats （P〈0.01）. TGF-#beta#1 and Snail1 protein expressions could not be detected by immunohistochemical staining in the normal renal tissues, however, the strongly positive staining was observed in diabetic rat renal tubules. A time-dependent loss of TGF-#beta#1 and Snail1 expressions was detected in the kidney of insulin-treated rats. In diabetic rats tubular #alpha##-SMA positive staining was seen at the 16th week. E-cadherin expression was lost in diabetic rats. The expressions of TGF-#beta#1, Snail1 proteins and Snail1 mRNA were significantly up-regulated in diabetic rats, while down-regulated in insulin-treated rats （P〈0.01）. The expressions of E-cadherin protein and mRNA in the cortex were contrary to the expressions of TGF-#beta#1 and Snail1. Therefore, TGF-#beta#1 and Snail1 are possibly involved in the pathogenesis of TEMT in diabetic nephropathy rats.

Key words: transforming growth factor-#beta#1;Snail1;E-cadherin;#alpha#-smooth muscle actin;diabetic nephropathy;Rat

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Citing This Article：

Fang Kaiyun, Lou Jinglei, Xiao Ying, Shi Mingjuan, Gui Huazhen, Guo Bing, Zhang Guozhong. Transforming growth factor--#beta#1 and Snail1 mediate tubular epithelial--mesenchymal transition in diabetic rats. Acta Physiol Sin 2008; 60 (1): 125-134 (in Chinese with English abstract).