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Microvasc Res. 2019 Mar 7;124:43-50. doi: 10.1016/j.mvr.2019.03.001. [Epub ahead of print]

miR-205-5p suppresses pulmonary vascular smooth muscle cell proliferation by targeting MICAL2-mediated Erk1/2 signaling.

Author information

1
Department of Breast Sugery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
2
Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: bym1505@126.com.

Abstract

Pulmonary arterial hypertension (PAH) is a devastating and fatal vascular disease for which currently there is no satisfying therapy available. Excessive cell proliferation of pulmonary arterial smooth muscle cells (PASMCs) contributes significantly to PAH pathogenesis. In this study, we found that miR-205-5p was lowly expressed in hypoxia-induced PAH mouse model and hypoxia-treated PASMCs. Restoration of miR-205-5p suppressed PASMCs proliferation. In contrast, molecule interacting with CasL 2 (MICAL2) was highly expressed in hypoxia-induced PAH mouse model and hypoxia-treated PASMCs. Overexpression of MICAL2 promoted cell proliferation. Furthermore, miR-205-5p inhibited MICAL2 expression levels by targeting the MICAL2 3' untranslated region. In addition, MICAL2 activated ERK1/2 signaling in PASMCs and ERK1/2 inhibitor blocked MICAL2-mediated-promotion effect on PASMCs proliferation. These results demonstrated that miR-205-5p suppressed PASMCs proliferation by targeting MICAL2, which activated ERK1/2 signaling. Therefore, miR-205-5p/MICAL2/Erk1/2 may serve as an ideal therapeutic target to PAH treatment.

KEYWORDS:

Erk1/2; MICAL2; Pulmonary arterial hypertension; Pulmonary arterial smooth muscle cells; miR-205-5p

PMID:
30853343
DOI:
10.1016/j.mvr.2019.03.001

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