MEIS1 regulated proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension

Abstract

AimProliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are regarded as the primary factors resulting in pulmonary arterial remodeling in pulmonary hypertension (PH). Myeloid ecotropic viral integration site 1 (MEIS1) has been positioned as a negative cardiomyocyte cell cycle regulator and regulates proliferation of multiple kinds of cancer cells. Whether MESI1 is involved in the proliferation and migration of PASMCs deserves to be identified. Main methodsSprague Dawley rats were exposed to hypoxia condition (10% O2) for 4 weeks to induce PH and primary rat PASMCs were cultured in hypoxia condition (3% O2) for 48 h to induce proliferation and migration. Immunohistochemistry, immunofluorescence, reverse transcription PCR and Western blot analysis were performed to detect the expressions of target mRNAs and proteins. EDU, CCK8 and wound healing assays were conducted to measure the proliferation and migration of PASMCs. Key findingsHypoxia down-regulated the expression of MEIS1 (both mRNA and protein) in pulmonary arteries and PASMCs. Over-expression of MEIS1 inhibited the proliferation and migration of PASMCs afforded by hypoxia. In contrast, knockdown of MEIS1 under normoxia condition like hypoxia induced the proliferation and migration of PASMCs. MEIS1 mediated hypoxia-induced the proliferation and migration of PASMCs via METTL14/MEIS1/p21 signaling. SignificanceThe present study revealed that MEIS1 regulated the proliferation and migration of PASMCs during hypoxia-induced PH. Thus, MEIS1 may be a potential target for PH therapy.