miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis

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 fibr...

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Published inInternational journal of molecular sciences Vol. 22; no. 19; p. 10574
Main Authors Hsu, Chih-Hsin, Liu, I-Fan, Kuo, Hsuan-Fu, Li, Chia-Yang, Lian, Wei-Shiung, Chang, Chia-Yuan, Chen, Yung-Hsiang, Liu, Wei-Lun, Lu, Chi-Yu, Liu, Yu-Ru, Lin, Tzu-Chieh, Lee, Tsung-Ying, Huang, Chi-Yuan, Hsieh, Chong-Chao, Liu, Po-Len
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2021
MDPI
Subjects
Apoptosis
Autophagy
Cardiac catheterization
Cardiomyocytes
Cardiomyopathy
Cell culture
Collagen
Fibroblasts
Flow velocity
Heart failure
Homeostasis
Intubation
Laboratory animals
Medical prognosis
Proteins
Pulmonary arteries
Stem cells
Veins & arteries
United States > US
Taiwan
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Summary: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.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms221910574