Wogonin protects against bleomycin-induced mouse pulmonary fibrosis via the inhibition of CDK9/p53-mediated cell senescence

• Published in: Frontiers in pharmacology Vol. 15; p. 1407891
• Main Authors: Wang, Libo, Lin, Fei, Liu, Youli, Li, Wei, Ding, Qingjie, Duan, Xulei, Yang, Lin, Bai, Zhengyu, Zhang, Min, Guo, Yuming
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.07.2024
• Subjects: bleomycin; cellular senescence; cyclin-dependent kinase; Pharmacology; pulmonary fibrosis; wogonin; bleomycin; cellular senescence; cyclin-dependent kinase; wogonin; pulmonary fibrosis
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2024.1407891

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from , owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. , wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated β-galactosidase (SA-β-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.