Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferation and the destruction of lung structure. Transforming growth factor-beta 1 (TGF-beta 1) is widely recognized as a central pathway of pulmonary fibrosis, and the suppression of TGF-beta 1 or the TGF-beta 1-regulated signaling pathway may thus offer potential antifibrotic therapies. JAK-STAT is a downstream signaling pathway regulated by TGF-beta 1. JAK1/2 inhibitor baricitinib is a marketed drug for the treatment of rheumatoid arthritis, but its role in pulmonary fibrosis has not been reported. This study explored the potential effect and mechanism of baricitinib on pulmonary fibrosis in vivo and in vitro. The in vivo studies have shown that baricitinib can effectively attenuate bleomycin (BLM)-induced pulmonary fibrosis, and in vitro studies showed that baricitinib attenuates TGF-beta 1-induced fibroblast activation and epithelial cell injury by inhibiting TGF-beta 1/non-Smad and TGF-beta 1/JAK/STAT signaling pathways, respectively. In conclusion, baricitinib, a JAK1/2 inhibitor, impedes myofibroblast activation and epithelial injury via targeting the TGF-beta 1 signaling pathway and reduces BLM-induced pulmonary fibrosis in mice.

Automated summary

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with unknown cause and limited treatment options. Transforming growth factor-beta 1 (TGF-beta 1) is recognized as a central pathway in pulmonary fibrosis. This study explored the potential effect and mechanism of JAK1/2 inhibitor baricitinib on reducing TGF-beta 1-induced fibroblast activation and epithelial injury, as well as attenuating bleomycin-induced pulmonary fibrosis in mice.