1. miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis
- Author
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Chih-Hsin Hsu, I-Fan Liu, Hsuan-Fu Kuo, Chia-Yang Li, Wei-Shiung Lian, Chia-Yuan Chang, Yung-Hsiang Chen, Wei-Lun Liu, Chi-Yu Lu, Yu-Ru Liu, Tzu-Chieh Lin, Tsung-Ying Lee, Chi-Yuan Huang, Chong-Chao Hsieh, and Po-Len Liu
- Subjects
miR-29a-3p ,THBS2 ,cardiomyocytes ,fibrosis ,pulmonary arterial hypertension ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.
- Published
- 2021
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