Get started
Work

miR-424/322 attenuates cardiac remodeling by modulating the nuclear factor-activated T-cell 3/furin pathway

Year: 2024
Type: article
Abstract: BACKGROUND: Cardiac remodeling is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure, and cardiac arrhythmias. Nuclear factor-activated T-cell cytoplasmic (NFATc) is a crucial transcription factor that regulates cardiac remodeling. MicroRNA (miR)-424/322 has pathophysiological roles in the cardiovascular and respiratory systems by modulating hypoxia and inflammatory pathways. The role of miR-424/322 in regulating cardiac remodeling is under investigation. We identified several cardiac hypertrophy and fibrosis-related molecules as putative targets of miR-424/322. We propose that miR-424/322 could have crucial roles in cardiac remodeling by modulating several key molecules for cardiac fibrosis and hypertrophy. METHODS: Human cardiac fibroblasts (HCFs) and a myogenic cell line H9c2 cells were used for in vitro experiments. A murine model of angiotensin II (AngII)-induced cardiac remodeling was used to assess the roles of miR-322 on cardiac hypertrophy and fibrosis in vivo. Immunoblotting, immunofluorescence, real-time polymerase chain reaction and cell proliferation, Sirius Red, and dual-luciferase reporter assays were used to decipher the molecular mechanism. RESULTS: We found that miR-322 knockout mice were susceptible to AngII-induced cardiac fibrosis and hypertrophy in vivo. Administration of miR-424/322 inhibitors aggravated AngII-induced overexpression of NFATc3, furin, natriuretic peptides and collagen 1A1 in H9c2 cells and HCFs. miR-424/322 mimics reversed the AngII-induced fibrosis, hypertrophy, and proliferation by targeting NFATc3 and furin in vitro. miR-424/322 could be transactivated by NFATc3. Exogenous miR-322 ameliorated AngII-induced hypertrophy and cardiac fibrosis in vivo. CONCLUSIONS: The NFATc3/miR-424/322/furin axis is crucial for developing cardiac remodeling, and exogenous miR-322 mimics could have therapeutic potential in cardiac remodeling.
DOI: 10.1016/j.bj.2024.100818
Authors: Hsiao-Ya Tsai, Jen-Chun Wang, Yu-Juei Hsu, Chih-Yuan Lin, Po-Hsun Huang, Min-Chien Tsai, Chin-Wang Hsu, Shang-Feng Yang, Shih-Hung Tsai
Institutions: Tri-Service General Hospital, National Defense Medical Center, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, Wan Fang Hospital, Taipei Medical University, Cheng Hsin General Hospital, Taichung Armed Forces General Hospital
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,700
Funders: National Science and Technology Council, National Defense Medical Center, Ministry of Science and Technology, Taiwan, Cheng Hsin General Hospital Foundation, Tri-Service General Hospital, National Science and Technology Council, Medical Affairs Bureau
Awards: G2097961618, G2312837402, G2348716235, G3224499615, The Association between Cold Weather and Acute Aortic Syndrome: the Roles of Cold-Inducible Rna-Binding Protein in Modulating the Oxidative Stress, a Bioinformatic, Animal and Mechanistical Study, G4876029608, Mir-424/322 Attenuates Cardiac Hypertrophy and Remodeling through Modulating Fibroblast-Mesenchymal Transition, Myofibroblast Proliferation and Nfatc Pathway., G521138584, G5274723103, G6254863792, The Roles of Nuclear Factor Activated T Cell Cytoplasmic (Nfatc)/Mir-615/ Myocyte Enhancer Factor 2 a (Mef2a) Axis in the Pathogenesis of Aortic Aneurysms : a New Therapeutic Target, G7672389879, G8217773461, G8975498276
OpenAlex ID: W4404657510
FWCI: 1.601
Cites: 53
Cited by: 6
Related to: 10