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Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell.


ABSTRACT: Ulcerative colitis (UC) is a recurrent intestinal inflammatory disease. Slit2, a secreted protein, interacts with its receptor Robo1 to regulate the differentiation of intestinal stem cells and participate in inflammation and tumor development. However, whether Slit2/Robo1involved in the pathogenesis of UC is not known. We investigated Slit2/Robo1-mediated UC using a dextran sodium sulfate (DSS)-induced model. Eight-week-old male Slit2-Tg (Slit2 transgene) mice, Robo1/2+/- (Robo1+/- Robo2+/-) mice, and their WT littermates were allocated into two groups: (I) control group (n=10), of mice fed a normal diet and tap water and (II) DSS group (n=10), of mice fed a normal diet and drinking water with 2% DSS for 7 days. Colon tissues were collected and analyzed by qPCR, immunohistochemistry, western blot, and immunofluorescence. Slit2-Tg DSS mice showed less body weight loss, less blood in the stool, and less viscous stool compared to those of WTSlit DSS mice. Robo1/2+/- DSS mice displayed a heavier degree of blood in the stool and a more apparent viscosity of the stool compared to those of WTRobo1/2 DSS mice. Slit2 overexpression maintained Lgr5+ stem cell proliferation in the crypt after DSS treatment, significantly increased the LC3II/I ratio, and slightly stimulated p62 expression in the crypt compared to those of DSS-induced WTSlit mice. Robo1/2 partial knockout reduced the number of Lgr5+ stem cells, decreased the LC3II/I ratio, and markedly increased p62 expression in the crypt compare to those of DSS-treated WTRobo1/2 mice. Our findings suggest that Slit2/Robo1 mediates DSS-induced UC probably by activating the autophagy of Lgr5+ stem cells.

SUBMITTER: Xie J 

PROVIDER: S-EPMC7211176 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell.

Xie Jingzhou J   Li Li L   Deng Shuhua S   Chen Jiayuan J   Gu Quliang Q   Su Huanhou H   Wen Lijing L   Wang Sheng S   Lin Caixia C   Qi Cuiling C   Zhang Qianqian Q   Li Jiangchao J   He Xiaodong X   Li Weidong W   Wang Lijing L   Zheng Lingyun L  

International journal of biological sciences 20200406 11


Ulcerative colitis (UC) is a recurrent intestinal inflammatory disease. Slit2, a secreted protein, interacts with its receptor Robo1 to regulate the differentiation of intestinal stem cells and participate in inflammation and tumor development. However, whether Slit2/Robo1involved in the pathogenesis of UC is not known. We investigated Slit2/Robo1-mediated UC using a dextran sodium sulfate (DSS)-induced model. Eight-week-old male Slit2-Tg (Slit2 transgene) mice, Robo1/2<sup>+/-</sup> (Robo1<sup>  ...[more]

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