干扰素调节因子5通过转录抑制Tgfbr1减轻纤维化
Xinyue Xu1, Mengqiu Miao1, Wenping Zhu1
1Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing 210008 China; Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing 210008 China; Jiangsu Key Laboratory of Early Development and Chronic Diseases Prevention in Children, Nanjing Medical University, Nanjing 210029 China.
International immunopharmacology
|January 19, 2025
概括
干扰素调节因子5 (IRF5) 在慢性病 (CKD) 中显示出抗纤维性作用. 激活IRF5可能为预防纤维化提供一种新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 管纤维化是慢性病 (CKD) 进展的关键因素.
- 干扰素调节因子5 (IRF5) 参与炎症和自身免疫性疾病.
- IRF5在CKD中的作用尚未在实验中得到证实.
研究的目的:
- 调查IRF5在纤维化病原发生中的作用.
- 探索IRF5作为CKD的潜在治疗点.
主要方法:
- 在人类CKD脏和纤维化小鼠模型中分析IRF5表达.
- 在体内研究使用单边尿路阻塞 (UUO) 的小鼠模型,具有Irf5敲击或过度表达.
- 在体外研究中使用TGF-β1刺激的细胞来评估IRF5.5的影响.
- 机制研究以阐明IRF5与TGF-β1/Smad3信号传递之间的相互作用.
主要成果:
- 在CKD患者和小鼠模型中,IRF5在纤维脏上调.
- 在UUO小鼠中,Irf5 knockdown 加重纤维化.
- 过度表达Irf5减弱了TGF-β1诱导的表皮细胞转移到介质细胞,内皮细胞介质细胞转移和纤维细胞激活.
- IRF5直接与Tgfbr1促进体结合,抑制其转录和亲纤维TGF-β1/Smad3通路.
结论:
- 通过抑制Tgfbr1.1,IRF5在细胞和纤维细胞中表现出抗纤维性作用.
- 激活IRF5为预防纤维化提供了一个新的治疗策略.
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