Dosage-dependent Role of RAC1 in Podocyte Injury.

Dosage-dependent Role of RAC1 in Podocyte Injury. Am J Physiol Renal Physiol. 2016 Jan 20;:ajprenal.00381.2015 Authors: Wan X, Lee MS, Zhou W Abstract Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase of Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly down-regulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage dependent manner and transgenic zebrafish of variable Rac1 activities in podocytes may serve a...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research