博莱霉素
肺纤维化
小檗碱
纤维化
上皮-间质转换
下调和上调
医学
药理学
肺
特发性肺纤维化
氧化应激
癌症研究
化学
内分泌学
内科学
生物化学
化疗
基因
作者
Omaima A. Ahmedy,Marwa Kamel,Dalia M. Abouelfadl,Marwa E. Shabana,Rabab H. Sayed
出处
期刊:Life Sciences
[Elsevier]
日期:2023-04-05
卷期号:322: 121665-121665
被引量:5
标识
DOI:10.1016/j.lfs.2023.121665
摘要
Berberine is endowed with anti-oxidant, anti-inflammatory and anti-fibrotic effects. This study explored the role of adenosine A2a receptor (A2aR) activation and SDF-1/CXCR4 signaling suppression in the protective effects of berberine in bleomycin-induced pulmonary fibrosis in mice.Pulmonary fibrosis was generated in mice by injecting bleomycin (40 U/kg, i.p.) on days 0, 3, 7, 10 and 14. Mice were treated with berberine (5 mg/kg, i.p.) from day 15 to day 28.Severe lung fibrosis and increased collagen content were observed in the bleomycin-challenged mice. Pulmonary A2aR downregulation was documented in bleomycin-induced pulmonary fibrosis animals and was accompanied by enhanced expression of SDF-1/CXCR4. Moreover, TGF-β1elevation and pSmad2/3 overexpression were reported in parallel with enhanced epithelial mesenchymal transition (EMT) markers expression, vimentin and α-SMA. Besides, bleomycin significantly elevated the inflammatory and pro-fibrogenic mediator NF-κB p65, TNF-α and IL-6. Furthermore, bleomycin administration induced oxidative stress as depicted by decreased Nrf2, SOD, GSH and catalase levels. Interestingly, berberine administration markedly ameliorated the fibrotic changes in lungs by modulating the purinergic system through the inhibition of A2aR downregulation, mitigating EMT and effectively suppressing inflammation and oxidative stress. Strikingly, A2aR blockade by SCH 58261, impeded the pulmonary protective effect of berberine.These findings indicated that berberine could attenuate the pathological processes of bleomycin-induced pulmonary fibrosis at least partially via upregulating A2aR and mitigating the SDF-1/CXCR4 related pathway, suggesting A2aR as a potential therapeutic target for the management of pulmonary fibrosis.
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