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Impact and significance of EGCG on Smad, ERK, and �²-catenin pathways in transdifferentiation of renal tubular epithelial cells

Author(s): C.G. Zhao, P. Zhou and Y.B. Wu

We investigated the impact and signal transduction mechanisms of epigallocatechin-3-gallate (EGCG) on transdiffer-entiation of renal tubular epithelial cells. Rat renal tubular epithelial cells (NRK-52E) were randomly divided into a normal control group, transforming growth factor (TGF)-b1-induced group (10 ng/mL), and intervention groups with 200 mg/L EGCG + 10 ng/mL TGF-b1 and 400 mg/L EGCG + 10 ng/mL TGF-b1. Tested cells were collected after 48 h. Levels of a-smooth muscle actin (α-SMA) and cytokeratin-18 were detected using immunohistochemical methods. Western blotting was used to detect cytoplasmic Pi-extracellular receptor kinase 1/2 (ERK1/2), Pi-Smad3 protein, and nuclear b-catenin protein. mRNA expression of ERK2, Smad3, and β-catenin was measured by reverse transcription-polymerase chain reaction. After induction by TGF-b1, cytokeratin-18 expression in the renal tubular epithelial cells decreased and a-SMA expression appeared. mRNA expression of cytoplasmic Pi-Smad3 and Pi-ERK1/2, Smad3, ERK2, and b-catenin protein expression increased, while β-catenin mRNA decreased. These changes were reduced after intervention by EGCG. EGCG may be helpful for maintaining the renal tubular epithelial cell phenotype and reducing the degree of TGF-b1- induced cell transdifferentiation, which may be related to the signal transduction pathway of ERK, Smad3, and b-catenin.