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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish
Zhao, Shaoyang; Xia, Jianhong; Wu, Xiuhua; Zhang, Leilei; Wang, Pengtao; Wang, Haiyun; Li, Heying; Wang, Xiaoshan; Chen, Yan; Agnetti, Jean; Li, Yinxiong; Pei, Duanqing; Shu, Xiaodong
2019-07-06
Source PublicationNATURE COMMUNICATIONS
Volume9
AbstractThe class III PI3-kinase (PIK3C3) is an enzyme responsible for the generation of phosphatidylinositol 3-phosphate (PI3P), a critical component of vesicular membrane. Here, we report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. In pik3c3 mutants, gut tube forms but fails to be maintained. Gene expression analysis reveals that barrier-function-related inflammatory bowel disease (IBD) susceptibility genes (e-cadherin, hnf4a, ttc7a) are suppressed, while inflammatory response genes are stimulated in the mutants. Histological analysis shows neutrophil infiltration into mutant intestinal epithelium and the clearance of gut microbiota. Yet, gut microorganisms appear dispensable as mutants cultured under germ-free condition have similar intestinal defects. Mechanistically, we show that PIK3C3 deficiency suppresses the formation of PI3P and disrupts the polarized distribution of cell-junction proteins in intestinal epithelial cells. These results not only reveal a role of PIK3C3 in gut homeostasis, but also provide a zebrafish IBD model.
Indexed BySCIE
Document Type期刊论文
Identifierhttp://ir.foo.ac.cn/handle/2SETSVCV/1471
Collection2018期刊论文
Recommended Citation
GB/T 7714
Zhao, Shaoyang,Xia, Jianhong,Wu, Xiuhua,et al. Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish[J]. NATURE COMMUNICATIONS,2019,9.
APA Zhao, Shaoyang.,Xia, Jianhong.,Wu, Xiuhua.,Zhang, Leilei.,Wang, Pengtao.,...&Shu, Xiaodong.(2019).Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish.NATURE COMMUNICATIONS,9.
MLA Zhao, Shaoyang,et al."Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish".NATURE COMMUNICATIONS 9(2019).
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