Long Noncoding RNA Tug1 Promotes Angiotensin II–Induced Renal Fibrosis by Binding to Mineralocorticoid Receptor and Negatively Regulating MicroR-29b-3p. Issue 3 (September 2021)

• Record Type: Journal Article
• Authors: Zhang, Juhong; Zhang, Yuqing; Gao, Jing; Wang, Meihui; Li, Xiaoting; Cui, Zhaoqiang; Fu, Guosheng
• Is Part Of: Hypertension. Volume 78:Issue 3(2021)
• Publication Date: 2021-09
• Subjects: aldosterone -- angiotensin -- fibrosis -- gene expression -- mineralocorticoids; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.120.16395
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.