MRTF-A mediated FN and ICAM-1 expression in AGEs-induced rat glomerular mesangial cells via activating STAT5

被引:10
作者
Chen, Qiuhong [1 ]
Huang, Junying [1 ]
Gong, Wenyan [1 ]
Chen, Zhiquan [1 ]
Huang, Jiani [1 ]
Liu, Peiqing [1 ,2 ]
Huang, Heqing [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Natl & Local United Engn Lab Druggabil & New Drug, Guangzhou 510006, Guangdong, Peoples R China
[3] Guangdong Prov Engn & Technol Res Ctr Dis Model A, Guangzhou 510006, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Diabetic nephropathy; AGEs; MRTF-A; STATs; STAT5; INTERCELLULAR-ADHESION MOLECULE-1; SERUM RESPONSE FACTOR; GLYCATION END-PRODUCTS; JAK/STAT-SIGNALING PATHWAY; DIABETIC-NEPHROPATHY; TRANSCRIPTION FACTORS; NRF2/ARE PATHWAY; RENAL-DISEASE; TRANSDUCER; MECHANISMS;
D O I
10.1016/j.mce.2017.07.014
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Advanced glycation end products (AGEs), formed at an accelerated rate under diabetes, play a role in inflammation and fibrosis in mesangial areas in diabetic nephropathy (DN). However, the transcriptional modulator that mediates the cellular response to AGEs remains largely obscure. Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, was responsible for the glomerular mesangial cells (GMCs) injury by AGEs, and, if so, how MRTF-A promoted mesangial dysfunction initiated by AGEs. In this study, MRTF-A was activated by AGEs in terms of protein expression and nuclear translocation in rat GMCs. MRTF-A overexpression synergistically enhanced the induction of FN and ICAM-1 by AGEs. In contract, depletion of MRTF-A abrogated the pathogenic program triggered by AGEs. Then, by interfering with MRTF-A, STAT1, STAT3 and STAT5 nuclear translocation were observed and we screened out STAT5, which was decreased obviously when MRTF-A depleted. Further investigation showed that MRTF-A interacted with STAT5 and promoted its nuclear accumulation and transcriptional activity. Therefore, our present findings suggested a role of MRTF-A in AGEs-induced GMCs injury, and further revealed that the underlying molecular mechanism was related to activating the nuclear factor STAT5. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:123 / 133
页数:11
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