Activation of Src-ATF1 pathway is involved in upregulation of Nox1, a catalytic subunit of NADPH oxidase, by aldosterone

Endocrine Journal

Chunyuan Fan⁵  Aiping Yin³  Wei Jiang⁵  Mei Feng⁵  Gang Shi⁵  Isamu Miyamori¹  Yasuyuki Kawai¹  Yanping Fu⁴  Yong Wu² 

[1] Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan;The second out-patient institutions of Chengdu Military Region, Chengdu, China;Department of Nephrology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an, China;Department of Nephrology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China;State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China

关键词: Aldosterone;    ROS;    Nox1;    Src;    ATF1;   

DOI  :  10.1507/endocrj.K10E-383

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(38)Cited-By(8)In this study, we mainly focused on how aldosterone regulates Nox1, a catalytic subunit of NADPH oxidase (NOX) in vascular smooth muscle cells (VSMC).We found that aldosterone can induce the expression of Nox1, which is upregulated by the activation of the Src and activating transcription factor 1 (ATF1), but can not be suppressed by the inhibitors of the epidermal growth factor receptor (EGFR) or Matrix Metalloproteinase (MMP).Aldosterone triggers ATF1 phosphorylation in dose dependent fashion, but this effect is not blocked by actinomycin D, suggesting a non-genomic effect of aldosterone.On the other hand, aldosterone induced Nox1 expression can be suppressed by the gene silencing of the ATF1 using RNA interference.Furthermore, silencing ATF1 can also attenuate aldosterone-induced O2- production and protein synthesis, and inhibit hypertrophy in this vascular cell lineage.In short, our results primarily unveiled the relationship between aldosterone and Nox1 expression and the regulation mechanism of their signal pathways in the hypertrophy of vascular smooth muscle cell.Src, ATF1, Nox1 and MR are likely efficient targets in the treating of vascular diseases but need more study.

【 授权许可】

Unknown