ArticleCardiovascular diagnosis and therapy2020
MicroRNA-221 promotes proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) by targeting tissue inhibitor of metalloproteinases-3 (TIMP3).
Article in Cardiovascular diagnosis and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Inhibiting HIF-1α-Induced miR-663b Improves Pulmonary Arterial Hypertension by Reducing Dysfunctions of PASMCs Through Repressing Sirt1-ZBP1-Mediated PANoptosis.Journal of cellular and molecular medicine · 2026Article
- Article
- Opposing roles for myeloid and smooth muscle cell STING in pulmonary hypertension.JCI insight · 2025Article
- Article
- Erratum to microRNA-221 promotes proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) by targeting tissue inhibitor of metalloproteinases-3 (TIMP3).Cardiovascular diagnosis and therapy · 2023Article
- Administration of A. muciniphila ameliorates pulmonary arterial hypertension by targeting miR-208a-3p/NOVA1 axis.Acta pharmacologica Sinica · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant vascular smooth muscle cell (VSMC) proliferation and migration play an important role in the development of cardiovascular diseases including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs, miRs) have been considered to be implicated in the progression of PAH pathogenesis. In this study, we aim to clarify the role of miR-221 on proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) and identify the target genes involved in this biological process.
methodsPASMCs were isolated from the pulmonary arteries of male Sprague-Dawley (SD) rats. Cell proliferation of PASMCs was detected by 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell migration was determined by a scratch wound assay. Quantitative real-time PCR was used to determine the expression of miR-221 while western blot analysis was used to determine the expression of TIMP3. Luciferase assay was used to confirm that TIMP3 was a direct target gene of miR-221. Monocrotaline (MCT) induced-PAH rat model was established and miR-221 and TIMP3 levels were checked in lung tissue and PASMCs from PAH rats.
resultsmiR-221 was able to promote the proliferation and migration PASMCs. TIMP3 were negatively regulated by miR-221 at the protein level in PASMCs. In addition, TIMP3 was identified to be a direct target gene of miR-221 in PASMCs based on luciferase assays. TIMP3 knockdown abolished the inhibitory effect of miR-221 inhibitor on PASMCs proliferation and migration, suggesting TIMP3 mediated the effects of miR-221 in PASMCs. Finally, we found that miR-221 was increased while TIMP3 was down-regulated in PASMCs in MCT-treated rats.
conclusionsIn conclusion, miR-221 promotes PASMCs proliferation and migration by targeting TIMP3. MiR-221 and TIMP3 could be potential therapeutic targets for the treatment of PAH.
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