| First Author | Wang L | Year | 2012 |
| Journal | Kidney Int | Volume | 81 |
| Issue | 11 | Pages | 1075-85 |
| PubMed ID | 22278020 | Mgi Jnum | J:278799 |
| Mgi Id | MGI:6359483 | Doi | 10.1038/ki.2011.472 |
| Citation | Wang L, et al. (2012) Mechanisms of the proteinuria induced by Rho GTPases. Kidney Int 81(11):1075-85 |
| abstractText | Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively active (V14 Rho) or dominant-negative Rho A (N19 Rho) in podocytes. Specific induction of either Rho A construct in podocytes caused albuminuria and foot process effacement along with disruption of the actin cytoskeleton as evidenced by decreased expression of the actin-associated protein synaptopodin. The mechanisms of these adverse effects, however, appeared to be different. Active V14 Rho enhanced actin polymerization, caused a reduction in nephrin mRNA and protein levels, promoted podocyte apoptosis, and decreased endogenous Rho A levels. In contrast, the dominant-negative N19 Rho caused a loss of podocyte stress fibers, did not alter the expression of either nephrin or Rho A, and did not cause podocyte apoptosis. Thus, our findings suggest that Rho A plays an important role in maintaining the integrity of the glomerular filtration barrier under basal conditions, but enhancement of Rho A activity above basal levels promotes podocyte injury. |
