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- Title
α(E)-catenin regulates BMP-7 expression and migration in renal epithelial cells.
- Authors
Nichols, LaNita A; Slusarz, Anna; Grunz-Borgmann, Elizabeth A; Parrish, Alan R
- Abstract
<bold>Background: </bold>The aging kidney has a decreased ability to repair following injury. We have shown a loss in expression of α-catenin in the aging rat kidney and hypothesize that decreased α-catenin expression in tubular epithelial cells results in diminished repair capacity.<bold>Methods: </bold>In an effort to elucidate alterations due to the loss of α-catenin, we generated NRK-52E cell lines with stable knockdown of α(E)-catenin.<bold>Results: </bold>α(E)-catenin knockdown resulted in decreased wound repair due to alterations in cell migration. Analysis of gene expression in the α(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 α(E)-catenin knockdown cells to control levels.<bold>Conclusions: </bold>Taken together, the data suggests that the loss of α(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.
- Publication
American Journal of Nephrology, 2014, Vol 39, Issue 4, p409
- ISSN
0250-8095
- Publication type
journal article
- DOI
10.1159/000362250