Effect of Mitofusin 2 on smooth muscle cells proliferation in hypoxic pulmonary hypertension

Mitofusin 2 (Mfn2) is an important mitochondrial protein in maintaining mitochondrial network and bioenergetics. Recently, Mfn2 has been reported to have a potential role in regulating cell proliferation, apoptosis, and differentiation in many cell types. In this study, we performed immunohistochemistry, pulmonary artery smooth muscle cells (PASMCs) DNA analysis, proliferating cell nuclear antigen expression and cell cycle analysis to determine the role of Mfn2 in hypoxia-induced pulmonary vascular remodeling. Our results showed that hypoxia promoted the proliferation of pulmonary artery smooth muscle cells, including regulating more cells at G(2)/M+S phase, increasing proliferating cell nuclear antigen and Cyclin A expression, whereas all these effects of hypoxia were suppressed after the cells were treated with siRNA against Mfn2. Our results also proved that PI3K/Akt signaling pathway was involved in Mfn2-induced smooth muscle cell proliferation. Thus, these results indicate that Mfn2 mediates PASMC proliferation in hypoxic pulmonary hypertension via the PI3K/Akt signaling pathway. (C) 2012 Elsevier Inc. All rights reserved.