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Parkin 通过自噬溶酶体降解下调 VDR 增加结肠炎的风险。

Parkin increases the risk of colitis by downregulation of VDR via autophagy-lysosome degradation.

机构信息

Key Laboratory of Immune Microenvironment and Disease, Department of Immunology, Nanjing Medical University, Nanjing211166, China.

Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing211166, China.

出版信息

Int J Biol Sci. 2023 Mar 5;19(5):1633-1644. doi: 10.7150/ijbs.77153. eCollection 2023.

DOI:10.7150/ijbs.77153
PMID:37056928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10086757/
Abstract

Parkin, an E3 ubiquitin ligase, plays an essential role in mitophagy. Emerging evidence indicates that mitophagy is involved in various processes closely related to immune diseases, including inflammatory bowel diseases (IBD). Here, the authors show that Parkin increases the occurrence of colitis and severe inflammation. Deletion of Parkin resulted in marked reductions in colonic inflammation and exhibited high resistance to DSS-induced colitis. Mechanism investigation indicated that Parkin interacts with Vitamin D receptors (VDR), a critical inhibitory regulator in IBD. Parkin promotes VDR degradation via the p62-related autophagy-lysosome pathway. Comparison of colitis in Parkin-/- and Parkin-/-Vdr-/- mice showed that the protective effect of Parkin deletion against colitis was abolished by VDR deletion. The result suggests that the regulatory effect of Parkin in colitis is a VDR-dependent pathway. Our research provides a new role of Parkin in colitis by downregulating VDR, which provides a potential strategy for treating IBD.

摘要

Parkin 是一种 E3 泛素连接酶，在自噬中发挥着重要作用。新出现的证据表明，自噬参与了与免疫疾病密切相关的各种过程，包括炎症性肠病（IBD）。在这里，作者表明 Parkin 增加了结肠炎和严重炎症的发生。Parkin 的缺失导致结肠炎症明显减少，并表现出对 DSS 诱导的结肠炎的高抵抗力。机制研究表明，Parkin 与维生素 D 受体（VDR）相互作用，VDR 是 IBD 的关键抑制调节因子。Parkin 通过 p62 相关的自噬溶酶体途径促进 VDR 的降解。Parkin-/-和 Parkin-/-Vdr-/-小鼠的结肠炎比较表明，VDR 缺失消除了 Parkin 缺失对结肠炎的保护作用。结果表明，Parkin 在结肠炎中的调节作用是一种依赖于 VDR 的途径。我们的研究通过下调 VDR 为治疗 IBD 提供了一种新的治疗策略，为 Parkin 在结肠炎中的作用提供了一个新的视角。

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Nix-Mediated Mitophagy Modulates Mitochondrial Damage During Intestinal Inflammation.Nix 介导的自噬调节肠道炎症期间的线粒体损伤。
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