Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Cell Prolif. 2022 May;55(5):e13222. doi: 10.1111/cpr.13222. Epub 2022 Apr 4.
Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease that poses a heavy burden to the global healthcare system. However, the current paucity of mechanistic understanding of IBD pathogenesis hampers the development of aetiology-directed therapies. Novel therapeutic options based on IBD pathogenesis are urgently needed for attaining better long-term prognosis for IBD patients. The tripartite motif (TRIM) family is a large protein family including more than 70 structurally conservative members, typically characterized by their RBCC structure, which primarily function as E3 ubiquitin ligases in post-translational modification. They have emerged as regulators of a broad range of cellular mechanisms, including proliferation, differentiation, transcription and immune regulation. TRIM family proteins are involved in multiple diseases, such as viral infection, cancer and autoimmune disorders, including inflammatory bowel disease. This review provides a comprehensive perspective on TRIM proteins' involvement in the pathophysiology and progression of IBD, in particular, on intestinal mucosal barriers, gene susceptibility and opportunistic infections, thus providing novel therapeutic targets for this complicated disease. However, the exact mechanisms of TRIM proteins in IBD pathogenesis and IBD-related carcinogenesis are still unknown, and more studies are warranted to explore potential therapeutic targets of TRIM proteins in IBD.
炎症性肠病(IBD)是一种慢性复发性胃肠道炎症性疾病,给全球医疗保健系统带来了沉重负担。然而,目前对 IBD 发病机制的机制理解不足,阻碍了病因导向治疗的发展。基于 IBD 发病机制的新治疗选择迫切需要为 IBD 患者实现更好的长期预后。TRIM 家族是一个包含 70 多个结构保守成员的大型蛋白质家族,通常以其 RBCC 结构为特征,主要作为翻译后修饰的 E3 泛素连接酶发挥作用。它们已成为多种细胞机制的调节剂,包括增殖、分化、转录和免疫调节。TRIM 家族蛋白参与多种疾病,如病毒感染、癌症和自身免疫性疾病,包括炎症性肠病。本综述全面阐述了 TRIM 蛋白在 IBD 的病理生理学和进展中的作用,特别是在肠道黏膜屏障、基因易感性和机会性感染方面,为这一复杂疾病提供了新的治疗靶点。然而,TRIM 蛋白在 IBD 发病机制和 IBD 相关癌变中的确切机制尚不清楚,需要更多的研究来探索 TRIM 蛋白在 IBD 中的潜在治疗靶点。