Abstract:

【Abstract】Objective: To investigate whether endothelin-1 (ET-1) could induce tubular epithelial-mesenchymal transition (TEMT）and the possible molecular mechanisms. Methodology: The rat renal tubular epithelial cells (NRK52E) were cultured in vitro and divided into several groups.The cells morphological changes were observed with inverted microscope. Western blot was used to assess the protein expression levels of E-cadherin, α-smooth muscle actin (α-SMA), p38mitogen-activated protein kinase (p38MAPK) and phosphorylated-p38MAPK (p-p38MAPK). RT-PCR was used to detect the mRNA expressions of E-cadherin and α-SMA. Results: The cobble-shaped renal tubular epithelial cells were induced to become fusiform by ET-1 which meanwhile down-regulated the expression of E-cadherin, whereas up-regulated the expressions of α-SMA, p38MAPK and p-p38MAPK and enhanced the activity of p38MAPK (P<0.05). All of these changes induced by ET-1 were obviously inhibited by the endothelin A receptor antagonists BQ123 (P<0.05). The p38MAPK specific inhibitor SB203580 also significantly inhibited the changes of morpholog of the cells, E-cadherin, α-SMA and p-p38MAPK expressions and p38MAPK activity induced by ET-1(P<0.05), but had no significant effect on the expression of p38MAPK (P>0.05). Conlusions: ET-1 can down-regulate the expressions of E-cadherin and up-regulate the expressions of α-SMA by activating the p38MAPK pathway in renal tubular epithelial cells, which then induces tubular epithelial cell transition.

Key words: 【Key Words】Endothelin-1;Renal tubular epithelial cell, Epithelial-mesenchymal transition, Renal interstitial fibrosi