博莱霉素
肺纤维化
转分化
安普克
肺
纤维化
特发性肺纤维化
医学
成纤维细胞
癌症研究
药理学
化学
蛋白激酶A
内科学
病理
磷酸化
体外
生物化学
化疗
作者
Wen Shi,Jiatong Hao,Yanliang Wu,Chang Liu,Kuniyoshi Shimizu,Renshi Li,Chaofeng Zhang
标识
DOI:10.1016/j.ejphar.2022.174825
摘要
Pulmonary fibrosis (PF) is a chronic interstitial lung disease with unknown etiology. In the present study, we evaluated the anti-fibrotic effects of heterophyllin B, a natural product from Radix Pseudostellariae having anti-inflammatory and tyrosinase inhibitory activities. In bleomycin (BLM)-induced PF mouse model, heterophyllin B treatments (5 or 20 mg/kg/d) significantly attenuated BLM-induced alveolar cavity collapse, inflammatory cell infiltration, alveolar wall thickening and collagen deposition. When compared to model group, heterophyllin B treatments also increased adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation levels by 359% (P < 0.001) and reduced the expression of stimulator of interferon genes (STING) by 73% (P < 0.001). Furthermore, co-administration of heterophyllin B with AMPK inhibitor dorsomorphin (Compound C) significantly blocked the improvement effects of heterophyllin B on BLM-damaged lung tissue, and also increased the protein expression of STING which was inhibited by heterophyllin B in fibrotic lungs (P < 0.001). It is known that alveolar epithelia and lung fibroblasts exert prominent roles in the fibrosis progression. In the present study we found that, in vitro, heterophyllin B significantly inhibited alveolar epithelial mesenchymal transition (EMT) and lung fibroblast transdifferentiation. We also found that the inhibition of heterophyllin B on lung fibroblast transdifferentiation and STING expression was reversed by Compound C. To summarize, heterophyllin B exhibited protective effects on BLM-induced lung fibrosis potentially by inhibiting TGF-Smad2/3 signalings and AMPK-mediated STING signalings.
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