Pleiotropic signaling evoked by tumor necrosis factor in podocytes.

Pleiotropic signaling evoked by tumor necrosis factor in podocytes. Am J Physiol Renal Physiol. 2015 May 27;:ajprenal.00146.2015 Authors: Abkhezr M, Kim EY, Roshanravan H, Nikilos F, Thomas C, Hagmann H, Benzing T, Dryer SE Abstract Tumor necrosis factor (TNF) has been implicated in glomerular diseases but its actions on podocytes are not well understood. Endogenous TNF expression is markedly increased in mouse podocytes exposed to sera from patients with recurrent focal and segmental glomerulosclerosis, and TNF is able to increase its own expression in these cells. Exposing podocytes to TNF increased phosphorylation of NFκB p65-RelA, followed by increased tyrosine phosphorylation of STAT3. STAT3 activation was blocked by the NFκB inhibitor JSH-23 and by the STAT3 inhibitor stattic, whereas TNF-evoked NFκB activation was not affected by stattic. TNF treatment increased nuclear accumulation of NFATc1 in podocytes, a process that occurred downstream of STAT3 activation. TNF also increased expression of cyclin D1, but had no effect on Cdk4, p27(kip), or podocin. In spite of its effects on cyclin D1, TNF treatment for up to 72 hr did not cause podocytes to re-enter the cell cycle. TNF increased total expression of TRPC6 channels through a pathway dependent on NFATc1, and increased the steady-state expression of TRPC6 subunits on the podocyte cell surface. TNF effects on TRPC6 trafficking required reactive oxygen species. Consistent wi...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research