¹Department of Nephrology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China

Correspondence: F-Y Liu, Department of Nephrology, the Second Xiangya Hospital of Central South University, Middle Ren-Min Road No.86, Changsha, Hunan 410011, China. E-mail: xiaozhaosun@hotmail.com

²These authors have contributed equally to this work.

Received 9 February 2007; Revised 13 September 2007; Accepted 25 September 2007; Published online 5 December 2007.

Abstract

Transforming growth factor- (TGF-) signaling has been linked with tubular epithelial to mesenchymal cell transition. In this study, we examined the role of Arkadia, an E3 ubiquitin ligase that is critically required for TGF- signaling during epithelial to mesenchymal cell transition. We found that when normal human renal tubular epithelial cells in culture were stimulated with TGF-1, which increased their levels of Arkadia, Smurf2, TGF- type I receptor (TRI), and Smad7 mRNA, but had low levels of Smad7 protein. When these cells were preincubated with Arkadia siRNA (small interfering RNA) and lactacystin (an inhibitor of proteasomal degradation), the TGF-₁ induced expression of Smad7, -smooth muscle actin, and E-cadherin was partly reversed, but the expression of TRI protein and Smad7 mRNA was not affected. In contrast, Smurf2 siRNA had no influence on the expression of these targets. Our studies suggest that Arkadia stimulates renal tubular epithelial to mesenchymal cell transition through degradation of Smad7.