The roles of Arkadia in renal tubular epithelial to mesenchymal transition.

The ubiquitin-proteasome pathway (UPP) can regulate the stability of proteins, which is regarded as an important mechanism in controlling various biological processes. In the pathway, E3 ubiquitin ligases play critical roles in the recognition of target proteins and degradation by 26S proteasomes. Arkadia is one of the E3 ubiquitin ligases, and recent research has shown that Arkadia amplifies TGF-beta signalling through degradation of Smad7. The cellular level of Smad7 plays an important role in the regulation of Smad-mediated TGF-beta signalling during progression of organ fibrosis. Studies indicate that the level of Smad7 protein expression is decreased in progression of tubulointerstitial fibrosis. Moreover, growing evidence suggests renal tubular epithelial to mesenchymal transition (EMT) plays a key role in renal tubulointerstitial fibrosis and transforming growth factor-beta(1) (TGF-beta(1)) is the most potent inducer that is capable of initiating and completing the entire EMT course. Therefore, the activation of Smad signalling induced by TGF-beta(1) plays a key role in the mechanism of renal tubular EMT, and in this process, Arkadia may has an important influence on the mechanism above mentioned through degradation of Smad7.