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Hepatocyte nuclear factor 4α negatively regulates STIM1 protein expression in human glomerular mesangial cells (689.15)
Author(s) -
Wang Yanxia,
Wu Peiwen,
Chaudhari Sarika,
Ma Rong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.689.15
Subject(s) - hepatocyte nuclear factor 4 , gene knockdown , transcription factor , hepatocyte nuclear factors , chromatin immunoprecipitation , microbiology and biotechnology , fibronectin , electrophoretic mobility shift assay , hepatocyte growth factor , chemistry , biology , gene expression , promoter , gene , nuclear receptor , receptor , biochemistry , extracellular matrix
Store‐operated Ca 2+ signaling pathway plays an important role in physiological and pathological processes in glomerular mesangial cells. STIM1 is a key component of this Ca 2+ entry pathway. We have recently demonstrated that high glucose (HG) significantly increased the expression level of STIM1 protein in cultured human mesangial cells (HMCs). However, the underlying mechanism for the HG response is unknown. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor expressed mainly in the kidney and liver, and regulates transcription of many genes. The present study was carried out to determine if HNF4α regulated STIM1 expression in response to HG treatment in HMCs. In cultured HMCs, HG treatment (25 mM for 6 days) significantly inhibited HNF4α‐DNA binding determined by electrophoretic mobility shift assay. Chromatin immunoprecipitation assays showed that HNF4α binding to STIM1 promoter region was attenuated by HG treatment. Knockdown of HNF4α using siRNA increased STIM1 mRNA and protein expressions. Furthermore, inhibition of store‐operated Ca 2+ entry or knockdown of STIM1 increased fibronectin and collagen IV protein expressions in HMCs. Knockdown of HNF4α decreased the expression levels of both fibronectin and collagen IV proteins. These results suggest that HNF4α represses STIM1 transcription in HMCs. Grant Funding Source : NIH/NIDDK