Impairment of HNF4α Binding to stim1 Promoter Contributes to High Glucose-induced Upregulation of STIM1 Expression in Glomerular Mesangial Cells.

Impairment of HNF4α Binding to stim1 Promoter Contributes to High Glucose-induced Upregulation of STIM1 Expression in Glomerular Mesangial Cells. Am J Physiol Renal Physiol. 2015 Mar 18;:ajprenal.00563.2014 Authors: Wang Y, Chaudhari S, Ren Y, Ma R Abstract The present study was carried out to investigate if hepatic nuclear factor 4α (HNF4α) contributed to high glucose-induced increase in STIM1 protein abundance in glomerular mesangial cells (MCs). Western blot and immunofluorescence studies showed HNF4α expression in MCs. Knockdown of HNF4α using siRNA approach significantly increased mRNA expression levels of both STIM1 and Orai1, and protein expression level of STIM1 in cultured human MCs. Consistently, over expression of HNF4α reduced expressed STIM1 protein expression in HEK293 cells. Furthermore, high glucose treatment did not significantly change abundance of HNF4α protein in MCs, but significantly attenuated HNF4α binding activity to stim1 promoter. Moreover, knockdown of HNF4α significantly augmented store-operated Ca2+ entry that is known to be gated by STIM1 and was recently found to be anti-fibrotic in MCs. In agreement with those results, knockdown of HNF4α significantly attenuated the fibrotic response of high glucose. These results suggest that HNF4α negatively regulates STIM1 transcription in MCs. High glucose increases STIM1 expression level by impairing HNF4α binding activity to stim1 promoter, which sub...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research