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miR-143 and miR-145 promote hypoxia-induced proliferation and migration of pulmonary arterial smooth muscle cells through regulating ABCA1 expression.
- Source :
-
Cardiovascular Pathology . Nov2018, Vol. 37, p15-25. 11p. - Publication Year :
- 2018
-
Abstract
- Abstract Background Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). miR-143/145 was reported to be up-regulated in the animal models and PAH patients, and deletion of miR-143/145 cluster prevented the development of hypoxia-induced pulmonary hypertension, but its underlying mechanism has not been elucidated. Methods qRT-PCR and Western blot were performed to detect the expressions of miR-143/145 and ATP-binding cassette transporter A1 (ABCA1) in PAH patients and PASMCs under hypoxic conditions. Cell proliferation and migration were assessed by Cell Counting Kit-8 and wound-healing assay, respectively. Luciferase reporter assay and RNA immunoprecipitation were conducted to confirm the interaction between miR-143/145 and ABCA1. Hypoxia-induced PAH rat model was established to confirm the functions of miR-143/145 in the pathogenesis of PAH and its underlying mechanism in vivo. Results miR-143 and miR-145 were up-regulated and ABCA1 was down-regulated in PAH patients and PASMCs under hypoxic conditions for different time, as well as hypoxia-induced PAH rats. miR-143/145 inhibition and ABCA1 overexpression suppressed hypoxia-induced proliferation and migration in PASMCs. ABCA1 was identified as a direct target of miR-143/145 in PASMCs. Moreover, ABCA1 partially reversed miR-143/145-mediated promotion of hypoxia-induced cell proliferation and migration in PASMCs. Furthermore, in vivo experiments confirmed that inhibition of miR-143/145 prevents hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling by targeting ABCA1. Conclusion miR-143/145 promoted hypoxia-induced proliferation and migration of PASMCs by targeting ABCA1, contributing to better understanding of the mechanism underlying the pathogenesis of PAH. Highlights • miR-143 and miR-145 were significantly up-regulated in PAH patients and hypoxia-treated PASMCs. • Inhibition of miR-143/145 suppressed hypoxia-induced proliferation and migration in PASMCs. • ABCA1 was a direct target of miR-143/145 in PASMCs. • ABCA1 overexpression impeded hypoxia-induced proliferation and migration in PASMCs. • ABCA1 partially reversed miR-143/145-mediated promotion of cell proliferation and migration in PASMCs exposed to hypoxia. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HYPOXEMIA
*MUSCLE cells
*MICRORNA
*PULMONARY artery
*CELL migration
Subjects
Details
- Language :
- English
- ISSN :
- 10548807
- Volume :
- 37
- Database :
- Academic Search Index
- Journal :
- Cardiovascular Pathology
- Publication Type :
- Academic Journal
- Accession number :
- 132992594
- Full Text :
- https://doi.org/10.1016/j.carpath.2018.08.003