TRIM65缺乏通过NUDT21介导的替代多基解来缓解纤维化
Sisi Wei1, Xuan Huang2, Qing Zhu2
1Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China.
Cell death and differentiation
|July 1, 2024
概括
E3结合酶TRIM65通过降解NUDT21,这是替代多基化的一个关键调节器,从而促进纤维化. 抑制TRIM65可能为慢性病 (CKD) 提供新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 腎病理生理學 腎病理生理學
- 生物化学 生物化学
背景情况:
- 慢性病 (CKD) 是一个全球性的健康问题,纤维化是其进展的主要驱动因素.
- 目前对纤维化机制的理解尚不完整,这限制了CKD患者的有效治疗选择.
- 之前还没有确定E3酶TRIM65在纤维化中的作用.
研究的目的:
- 研究E3结合酶TRIM65在纤维化发展中的作用.
- 确定TRIM65的新型相互作用体,并阐明它们在纤维化中的功能.
- 探索针对TRIM65进行治疗性干预的潜力.
主要方法:
- 使用了由单边尿路阻塞 (UUO) 和叶酸诱导的纤维化的小鼠模型.
- 采用酵母混合系统选TRIM65相互作用体,识别NUDT21.
- 研究了TRIM65对NUDT21的无处不在和降解及其对信号通路和3'UTR替代多基解 (APA) 的影响.
主要成果:
- 在小鼠模型中,TRIM65的删除显著减少了病理病变和纤维化.
- TRIM65与NUDT21相互作用,促进其K48结合的多比基因化和蛋白质体降解.
- 通过TRIM65降解NUDT21,改变亲纤维基因的3'UTR-APA,影响TGF-β1和ERK1/2信号传递.
结论:
- TRIM65通过控制NUDT21介导的替代多基化,作为纤维化的积极调节剂.
- 由TRIM65诱导的NUDT21降解会影响关键的亲纤维细胞信号通路.
- 在慢性病中,TRIM65是缓解纤维化的有前途的治疗标.
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