The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.
The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease.
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DOI：
10.3390/biomedicines11072066
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发表时间：
2023-07-23
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
内质网（ER）是一种多功能的细胞器，在维持细胞内稳态中起着至关重要的作用，其功能的破坏会对细胞产生有害影响。ER应激和未折叠蛋白反应（UPR）失调与多种人类疾病有关。例如，ER应激和肠上皮细胞中UPR信号通路的激活可以加剧或减轻炎症性肠病（IBD）的严重程度，取决于激活的程度和条件。我们最近的研究表明，EPICERTIN，一种含有ER滞留基序的霍乱毒素B亚基的重组变体，可以诱导结肠上皮细胞中的保护性UPR，随后促进IBD模型中的上皮修复和粘膜愈合。这些发现支持了这样的想法，即调节UPR的化合物可能是治疗该疾病的有希望的候选药物。本文综述了炎症性肠病中内质网应激和UPR的研究进展，重点介绍了它们在维持细胞稳态、调节异常和疾病发病机制中的作用。此外，我们还讨论了通过药理学操作UPR来促进结肠上皮细胞的细胞保护和减少炎症的治疗策略。
The endoplasmic reticulum (ER) is a multifunctional organelle playing a vital role in maintaining cell homeostasis, and disruptions to its functions can have detrimental effects on cells. Dysregulated ER stress and the unfolded protein response (UPR) have been linked to various human diseases. For example, ER stress and the activation of the UPR signaling pathways in intestinal epithelial cells can either exacerbate or alleviate the severity of inflammatory bowel disease (IBD), contingent on the degree and conditions of activation. Our recent studies have shown that EPICERTIN, a recombinant variant of the cholera toxin B subunit containing an ER retention motif, can induce a protective UPR in colon epithelial cells, subsequently promoting epithelial restitution and mucosal healing in IBD models. These findings support the idea that compounds modulating UPR may be promising pharmaceutical candidates for the treatment of the disease. In this review, we summarize our current understanding of the ER stress and UPR in IBD, focusing on their roles in maintaining cell homeostasis, dysregulation, and disease pathogenesis. Additionally, we discuss therapeutic strategies that promote the cytoprotection of colon epithelial cells and reduce inflammation via pharmacological manipulation of the UPR.
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