SREBP Inhibition Ameliorates Renal Injury after Unilateral Ureteral Obstruction.

SREBP Inhibition Ameliorates Renal Injury after Unilateral Ureteral Obstruction. Am J Physiol Renal Physiol. 2016 Jul 6;:ajprenal.00140.2016 Authors: Mustafa M, Wang TN, Chen X, Gao B, Krepinsky JC Abstract Tubulointerstitial fibrosis is a major feature associated with declining kidney function in chronic kidney disease of diverse etiology. No effective means as yet exists to prevent the progression of fibrosis. We have shown that the transcription factor SREBP-1 is an important mediator of the profibrotic response to TGFβ and Angiotensin II, both key cytokines in the fibrotic process. Here we examined the role of SREBP in renal interstitial fibrosis in the unilateral ureteral obstruction (UUO) model. The two isoforms of SREBP (-1 and -2) were activated by 3 days after UUO, with SREBP-1 showing a more sustained activation to 21 days. We then examined whether SREBP1/2 inhibition with the small molecule inhibitor fatostatin could attenuate fibrosis after 14 days of UUO. SREBP activation was confirmed to be inhibited by fatostatin. Treatment decreased interstitial fibrosis, TGFβ signaling, and upregulation of αSMA, a marker of fibroblast activation. Fatostatin also attenuated inflammatory cell infiltrate and apoptosis. Associated with this, fatostatin preserved proximal tubular mass. The significant increase in atubular glomeruli observed after UUO, known to correlate with irreversible renal functional decline, was also decreased by ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research