Idiopathic pulmonary fibrosis (IPF) is a fatal age-related chronic lung disease, characterized by progressive scarring of the lungs by activated fibroblasts. The effect of omentin-1 against pulmonary fibrosis and fibroblast activation has not been investigated. The purpose of this experiment is to investigate the role of omentin-1 in bleomycin (BLM)-induced lung fibrosis and its mechanism. Our results showed that the loss of omentin-1 exaggerated lung fibrosis induced by BLM. On the contrary, adenoviral-overexpression of omentin-1 significantly alleviated BLM-induced lung fibrosis both in preventive and therapeutic regimens. Moreover, omentin-1 prevented fibroblast activation determined by a decreased number of S100A4+ (fibroblasts marker) α-SMA+ cells in vivo, and a decreased level of α-SMA expression both in mice primary fibroblasts and human primary fibroblasts induced by TGF-β in vitro. Furthermore, the phosphorylation of AMP-activated protein kinase (p-AMPK) was significantly lower in the fibrotic foci induced by BLM, and the adenoviral-overexpression of omentin-1 significantly increased the p-AMPK level in vivo. Importantly, Compound C, the inhibitor of AMPK, significantly attenuated the protective effect of omentin-1 on BLM-induced lung fibrosis and reversed the effect of omentin-1 on fibroblast activation by TGF-β. Omentin-1 can be a promising therapeutic agent for the prevention and treatment of lung fibrosis.
Keywords: AMPK pathway; bleomycin; fibroblast activation; lung fibrosis; myofibroblast; omentin-1.