Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression

Context: Fibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF.Objective: This study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence.Materials and methods: Institute of Cancer Research (ICR) mice were randomly assigned to control, bleomycin (BLM), baicalein and BLM + baicalein groups. Lung fibrosis was established by a single intratracheal dose of BLM (3 mg/kg). The baicalein group received baicalein orally (100 mg/kg/day). Sirtuin 3 (Sirt3) siRNA (50 mu g) was injected through the tail vein once a week for 2 weeks to explore its effect on the anti-pulmonary fibrosis of baicalein.Results: BLM-treated mice exhibited obvious lung fibrosis and fibroblast senescence by showing increased levels of collagen deposition (27.29% vs. 4.14%), hydroxyproline (208.05 vs. 40.16 ng/mg), collagen I (25.18 vs. 9.15 mu g/mg), p53, p21, p16, MCP-1, PAI-1, TNF-alpha, MMP-10 and MMP-12 in lung tissues, which were attenuated by baicalein. Baicalein also mitigated BLM-mediated activation of TGF-beta 1/Smad signalling pathway. Baicalein restored the BLM-induced downregulation of Sirt3 expression in lung tissues and silencing of Sirt3 abolished the inhibitory role of baicalein against BLM-induced lung fibrosis, fibroblast senescence and activation of TGF-beta 1/Smad signalling pathway.Conclusions: Baicalein preserved the BLM-induced downregulation of lung Sirt3 expression, and thus the suppression of TGF-beta 1/Smad signalling pathway and lung fibrosis, which might provide an experimental basis for treatment of IPF.

Automated summary

This study investigates whether baicalein can attenuate lung fibrosis by regulating lung fibroblast senescence. The results suggest that baicalein can mitigate lung fibrosis, fibroblast senescence, and activation of the TGF-beta 1/Smad signaling pathway.