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

Aim: Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are regarded as the pri- mary 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 reg- ulates proliferation of multiple kinds of cancer cells. Whether MESI1 is involved in the proliferation and mi- gration of PASMCs deserves to be identified. Main methods: Sprague 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 per- formed 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 findings: Hypoxia 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 hy- poxia. 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. Significance: The 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. 1.