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

Xie, Jingzhou; Li, Li; Deng, Shuhua; Chen, Jiayuan; Gu, Quliang; Su, Huanhou; Wen, Lijing; Wang, Sheng; Lin, Caixia; Qi, Cuiling; Zhang, Qianqian; Li, Jiangchao; He, Xiaodong; Li, Weidong; Wang, Lijing; Zheng, Lingyun

doi:10.7150/ijbs.42331

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Int J Biol Sci 2020; 16(11):1876-1887. doi:10.7150/ijbs.42331 This issue Cite

Research Paper

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

Jingzhou Xie^1#, Li Li^1#, Shuhua Deng^1#, Jiayuan Chen¹, Quliang Gu¹, Huanhou Su¹, Lijing Wen¹, Sheng Wang¹, Caixia Lin¹, Cuiling Qi¹, Qianqian Zhang¹, Jiangchao Li¹, Xiaodong He¹, Weidong Li^2,3, Lijing Wang^1✉, Lingyun Zheng^1✉

1. School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, PR China.
2. Institute of Health, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, P. R. China.
3. Guangdong Engineering Research Center for Light and Health, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, P. R. China.
#These authors contributed equally to this work.

Citation:

Xie J, Li L, Deng S, Chen J, Gu Q, Su H, Wen L, Wang S, Lin C, Qi C, Zhang Q, Li J, He X, Li W, Wang L, Zheng L. Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell. Int J Biol Sci 2020; 16(11):1876-1887. doi:10.7150/ijbs.42331. https://www.ijbs.com/v16p1876.htm

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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 WT_Slit 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 WT_Robo1/2 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 WT_Slit 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 WT_Robo1/2 mice. Our findings suggest that Slit2/Robo1 mediates DSS-induced UC probably by activating the autophagy of Lgr5⁺ stem cells.

Keywords: Slit2/Robo1 signal, UC, autophagy, Lgr5 stem cells

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APA

Xie, J., Li, L., Deng, S., Chen, J., Gu, Q., Su, H., Wen, L., Wang, S., Lin, C., Qi, C., Zhang, Q., Li, J., He, X., Li, W., Wang, L., Zheng, L. (2020). Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell. International Journal of Biological Sciences, 16(11), 1876-1887. https://doi.org/10.7150/ijbs.42331.

ACS

Xie, J.; Li, L.; Deng, S.; Chen, J.; Gu, Q.; Su, H.; Wen, L.; Wang, S.; Lin, C.; Qi, C.; Zhang, Q.; Li, J.; He, X.; Li, W.; Wang, L.; Zheng, L. Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell. Int. J. Biol. Sci. 2020, 16 (11), 1876-1887. DOI: 10.7150/ijbs.42331.

NLM

CSE

Xie J, Li L, Deng S, Chen J, Gu Q, Su H, Wen L, Wang S, Lin C, Qi C, Zhang Q, Li J, He X, Li W, Wang L, Zheng L. 2020. Slit2/Robo1 Mitigates DSS-induced Ulcerative Colitis by Activating Autophagy in Intestinal Stem Cell. Int J Biol Sci. 16(11):1876-1887.

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