Resistin-like molecule ? acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK signaling pathways

Abstract Background Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule ? (RELM-?) is upregulated de novo response to hypoxia cultured human PASMCs (hPASMCs). RELM-? has been reported promote hPASMC and involved vascular remodeling patients with PAH. However, the expression pattern, effects, mechanisms of action HPH remain unclear. Methods We assessed mitogenetic effect, mechanism rat model hPASMCs. Results Overexpression caused hemodynamic changes similar those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), hypertrophy index (RVH I ) thickening small arterioles. Knockdown partially blocked increases mRVSP, RVHI, hypoxia. The phosphorylation levels PI3K, Akt, mTOR, PKC, MAPK proteins were significantly up- or downregulated gene overexpression silencing, respectively. Recombinant protein intracellular Ca 2+ concentration primary hPASMCs promoted proliferation. mitogenic effects on suppressed inhibitor. Conclusions Our findings suggest acts as cytokine-like growth factor development are likely be mediated -dependent PI3K/Akt/mTOR PKC/MAPK pathways.