P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium.
P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium.
复制标题
P62/SQSTM1与claudin-2结合，靶向应激状态下肠上皮细胞的选择性自噬。
DOI：
10.1038/s42003-023-05116-2
复制
发表时间：
2023-07-17
影响因子：
5.9
通讯作者：
Singh, Amar B.
中科院分区：
文献类型：
--
作者：
Ahmad, Rizwan;Kumar, Balawant;Tamang, Raju Lama;Talmon, Geoffrey A.;Dhawan, Punita;Singh, Amar B.
受损的自噬促进炎症性肠病（IBD）。Claudin-2在IBD中上调，但由于其复杂的调控，包括自噬，其在病理生物学中的作用仍然不确定。无论如何，claudin-2表达保护小鼠免受DSS结肠炎。这项研究旨在研究自噬和claudin-2之间的相互作用是否可以防止结肠炎和相关的上皮损伤。隐窝培养物和肠上皮细胞（IEC）受到应激，包括饥饿或DSS，DSS是体内诱导结肠炎的化学物质。进行自噬通量、细胞存活、免疫共沉淀、邻近连接测定和基因突变研究。这些研究表明，在结肠炎/应激条件下，claudin-2通过自噬进行多聚泛素化和P62/SQSTM 1辅助降解。抑制自噬介导的claudin-2降解促进细胞死亡，因此表明claudin-2降解促进自噬通量以促进细胞存活。总的来说，这些数据为以前未描述的claudin-2在促进IEC在应激条件下存活的作用提供了信息，这可以用于治疗优势。在包括结肠炎在内的应激下，claudin-2蛋白通过P62/SQSTM 1辅助的自噬降解，以促进肠上皮细胞的存活。减少的claudin-2表达和增加的细胞存活反过来改善了肠道屏障的完整性。
Impaired autophagy promotes Inflammatory Bowel Disease (IBD). Claudin-2 is upregulated in IBD however its role in the pathobiology remains uncertain due to its complex regulation, including by autophagy. Irrespective, claudin-2 expression protects mice from DSS colitis. This study was undertaken to examine if an interplay between autophagy and claudin-2 protects from colitis and associated epithelial injury. Crypt culture and intestinal epithelial cells (IECs) are subjected to stress, including starvation or DSS, the chemical that induces colitis in-vivo. Autophagy flux, cell survival, co-immunoprecipitation, proximity ligation assay, and gene mutational studies are performed. These studies reveal that under colitis/stress conditions, claudin-2 undergoes polyubiquitination and P62/SQSTM1-assisted degradation through autophagy. Inhibiting autophagy-mediated claudin-2 degradation promotes cell death and thus suggest that claudin-2 degradation promotes autophagy flux to promote cell survival. Overall, these data inform for the previously undescribed role for claudin-2 in facilitating IECs survival under stress conditions, which can be harnessed for therapeutic advantages. Under stress including colitis, claudin-2 protein is degraded by P62/SQSTM1-assisted autophagy to promote survival of intestinal epithelial cells. Decreased claudin-2 expression and increased cell survival in turn improves the gut barrier integrity.
登录
查看更多内容
PKCι与RAB14相互作用，并通过调节Claudin-2水平来调节上皮屏障功能。
影响因子：
3.3
作者：
Lu R;Dalgalan D;Mandell EK;Parker SS;Ghosh S;Wilson JM
通讯作者：
Wilson JM
影响因子：
13.3
作者：
Ganapathy, Ashwinkumar Subramenium;Saha, Kushal;Nighot, Prashant
通讯作者：
Nighot, Prashant
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
29.4
作者：
Homer CR;Richmond AL;Rebert NA;Achkar JP;McDonald C
通讯作者：
McDonald C
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ