Mammalian target of rapamycin complex 1 activation in podocytes promotes cellular crescent formation.

Mammalian target of rapamycin complex 1 activation in podocytes promotes cellular crescent formation. Am J Physiol Renal Physiol. 2014 Jul 2; Authors: Mao J, Zeng Z, Xu Z, Li J, Jiang L, Fang Y, Xu X, Hu Z, He W, Yang J, Dai C Abstract Abstract Podocytes play a key role in the formation of cellular crescents in experimental and human diseases. However, the underlying mechanisms for podocytes in promoting crescent formation need further investigation. Here we demonstrated that mammalian target of rapamycin complex 1 (mTORC1) signaling was remarkably activated and HIF1alpha expression was largely induced in cellular crescents from patients with crescentic glomerular diseases. Specific deletion of Tsc1 in podocytes led to mTORC1 activation in podocytes and kidney dysfunction in mice. Interestingly, 33 of 36 knockouts developed cellular or mixed cellular and fibrous crescents at 7 weeks of age (14.19±3.86% of total glomeruli in knockouts vs 0% in control littermates, n=12-36, P=0.04). All of the 7 knockouts developed crescents at 12 weeks of age (30.92±11.961% of total glomeruli in knockouts vs 0% in control littermates n=4-7, P=0.002). Most notably, bridging cells between the glomerular tuft and the parietal basement membrane as well as the cellular crescents were immunostaining positive for WT1, p-S6, HIF1alpha and Cxcr4. Furthermore, continuously administrating rapamycin started at 7 weeks of age for 5 weeks abolished crescent as we...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research