Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice

Laboratory Investigation; a Journal of Technical Methods and Pathology
Yinzhong ZhangPing Wang

Abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the digestive system and typically requires lifelong medical care. Recombinant human MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell clearance and reduces inflammation. This study investigates the therapeutic effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or 120 μg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8 significantly attenuated colitis in both models in a dose-dependent way. Treatment of DSS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8 (120 μg/kg/day) decreased weight loss by 97%, the colitis severity score by ...Continue Reading

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Citations

Feb 18, 2016·The Journal of Nutritional Biochemistry·Bidya Dhar SahuRamakrishna Sistla
Aug 20, 2015·Nature Immunology·Sanja Arandjelovic, Kodi S Ravichandran
Jan 14, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiangming DingQin Yu
Apr 28, 2020·The Journal of the American Osteopathic Association·Artur SchanderLisa M Hodge
Sep 1, 2016·BoneKEy Reports·Kathrin SinningenMartina Rauner
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Feb 17, 2018·ACS Biomaterials Science & Engineering·Hyesun HyunYoon Yeo

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