期刊
Hypertension
标题
Long Noncoding RNA Tug1 Promotes Angiotensin II–Induced Renal Fibrosis by Binding to Mineralocorticoid Receptor and Negatively Regulating MicroR-29b-3p
作者
Juhong Zhang, Yuqing Zhang, Jing Gao, Meihui Wang, Xiaoting Li, Zhaoqiang Cui and Guosheng Fu
摘要
Inappropriately activation of renin-angiotensin-aldosterone system induced renal fibrosis is characterized by partial epithelial-to-mesenchymal transition. Previously, we have indicated that miR-29b-3p in inhibiting partial epithelial-to-mesenchymal transition by negatively regulating extracellular matrix gene expression in the kidney. Despite the critical role of miR-29b-3p in fibrosis, the molecular mechanisms by which miR-29b-3p is regulated under the condition of profibrotic stimuli are largely unknown. Our aim is to search for the long noncoding RNA that mediated sponge regulatory on miR-29b-3p, and whether the long noncoding RNA could be activated by renin-angiotensin-aldosterone system and its consequent effects on renal fibrosis. Bioinformatics analysis predicted that Tug1 might directly bound to miR-29b-3p and function as a competing endogenous RNA. Dual-luciferase reporter assay, fluorescence in situ hybridization, and real-time polymerase chain reaction were performed to indicate that Tug1 interact with miR-29b-3p in a sequence-specific manner. Decreased Tug1 led to an increase in extracellular matrix measured by Western blot, and this effect was enhanced by miR-29b-3p measured by real-time polymerase chain reaction and Western blot, suggesting cross-regulation between the RNAs. Bioinformatics analysis predicted that mineralocorticoid receptor might bind to long noncoding RNA Tug1. Notably, mineralocorticoid receptor antagonism reduced Tug1 expression in the presence or absence of angiotensin II or aldosterone measured by real-time polymerase chain reaction, and RNA immunoprecipitation assays confirmed that the mineralocorticoid receptor directly bound to Tug1. Finally, we confirmed that Tug1 expression was enhanced in fibrotic compared with nonfibrotic human renal biopsy samples using RNA-in situ hybridization. Our findings provide novel insights into the molecular mechanism of Ang II–induced renal fibrosis and identify the Tug1–miR-29b-3p axis as an important target of MR activation.
原文链接
https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.16395
