α(E)-catenin regulates BMP-7 expression and migration in renal epithelial cells.

Background: The aging kidney has a decreased ability to repair following injury. We have shown a loss in expression of alpha-catenin in the aging rat kidney and hypothesize that decreased alpha-catenin expression in tubular epithelial cells results in diminished repair capacity. Methods: In an effort to elucidate alterations due to the loss of alpha-catenin, we generated NRK-52E cell lines with stable knockdown of alpha(E)-catenin. Results: alpha(E)-catenin knockdown resulted in decreased wound repair due to alterations in cell migration. Analysis of gene expression in the alpha(E)-catenin knockdown cells demonstrated almost a complete loss of bone morphogenetic protein-7 (BMP-7) expression that was associated with decreased phospho-Smad1/5/8 staining. However, addition of exogenous BMP-7 increased phospho-Smad1/5/8, suggesting that the BMP-7 pathway remained intact in C2 cells. Given the potential role of BMP-7 in repair, we investigated its role in wound repair. Inhibition of BMP-7 decreased repair in non-targeted control cells; conversely, exogenous BMP-7 restored repair in alpha(E)-catenin knockdown cells to control levels. Conclusions: Taken together, the data suggests that the loss of alpha(E)-catenin expression and subsequent downregulation of BMP-7 is a mechanism underlying the altered migration of tubular epithelial cells that contributes to the inability of the aging kidney to repair following injury. (C) 2014 S. Karger AG, Basel