| Title | FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis |
| Authors | Liang, Weiwei Peng, Xinjian Li, Qingqing Wang, Pingzhang Lv, Ping Song, Quansheng She, Shaoping Huang, Shiyang Chen, Keqiang Gong, Wanghua Yuan, Wuxing Thovarai, Vishal Yoshimura, Teizo O'huigin, Colm Trinchieri, Giorgio Huang, Jiaqiang Lin, Shuye Yao, Xiaohong Bian, Xiuwu Kong, Wei Xi, Jianzhong Wang, Ji Ming Wang, Ying |
| Affiliation | Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100191, Peoples R China Peking Univ, NHC Key Lab Med Immunol, Beijing 100191, Peoples R China NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA Leidos Biomed Res Inc, Basic Res Program, Frederick, MD 21702 USA Leidos Biomed Res Inc, Microbiome Sequencing Core, Frederick, MD 21702 USA Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med, Okayama 7008558, Japan Capital Med Univ, Beijing Chest Hosp, Canc Res Ctr, Beijing TB & Thorac Tumor Res Inst, Beijing 101149, Peoples R China South West Hosp & Canc Ctr, Inst Pathol, Chongqing, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China Peking Univ, Dept Biomed, Coll Engn, Beijing 100871, Peoples R China |
| Keywords | INTESTINAL EPITHELIAL-CELLS FORMYL PEPTIDE RECEPTOR MICROBIOTA COLITIS CANCER BARRIER IDENTIFICATION RESTITUTION EXPRESSION PROTEOMICS |
| Issue Date | 20-Nov-2020 |
| Publisher | NATURE COMMUNICATIONS |
| Abstract | The physiological homeostasis of gut mucosal barrier is maintained by both genetic and environmental factors and its impairment leads to pathogenesis such as inflammatory bowel disease. A cytokine like molecule, FAM3D (mouse Fam3D), is highly expressed in mouse gastrointestinal tract. Here, we demonstrate that deficiency in Fam3D is associated with impaired integrity of colonic mucosa, increased epithelial hyper-proliferation, reduced anti-microbial peptide production and increased sensitivity to chemically induced colitis associated with high incidence of cancer. Pretreatment of Fam3D(-/-) mice with antibiotics significantly reduces the severity of chemically induced colitis and wild type (WT) mice co-housed with Fam3D(-/-) mice phenocopy Fam3D-deficiency showing increased sensitivity to colitis and skewed composition of fecal microbiota. An initial equilibrium of microbiota in cohoused WT and Fam3D(-/-) mice is followed by an increasing divergence of the bacterial composition after separation. These results demonstrate the essential role of Fam3D in colon homeostasis, protection against inflammation associated cancer and normal microbiota composition. The cytokine like protein FAM3D (Fam3D in mice) is highly expressed in the digestive tract with unknown role in colon pathophysiology. Here, by using gene deficient mice, the authors show that Fam3D is critically involved in colon homeostasis, host defense against colitis-associated carcinogenesis, and the balance of microbiota. |
| URI | http://hdl.handle.net/20.500.11897/599886 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-020-19691-z |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 工学院 |
