title: GYY4137 ameliorates intestinal barrier injury in a mouse model of endotoxemia.
abstract: Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H2S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF-α/IFN-γ and a mouse model of endotoxemia were used in this study. The results suggested that GYY4137 significantly attenuated LPS or TNF-α/IFN-γ induced increased Caco-2 monolayer permeability. The decreased expression of TJ (tight junction) proteins induced by LPS and the altered localization of TJs induced by TNF-α/IFN-γ was significantly inhibited by GYY4137; similar results were obtained in vivo. Besides, GYY4137 promoted the clinical score and histological score of mice with endotoxemia. Increased level of TNF-α/IFN-γ in the plasma and increased apoptosis in colon epithelial cells was also attenuated by GYY4137 in mice with endotoxemia. This study indicates that GYY4137 preserves the intestinal barrier function in the context of endotoxemia via multipathways and throws light on the development of potential therapeutic approaches for endotoxemia.
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Shanwen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Central Laboratory, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.affiliation: Animal Experiment Center, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Lie
authors.initials: L
authors.lastname: Sun
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Ju
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Tengyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Zeyang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China. Electronic address: wangpengyuan2014@126.com.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Division of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing 100034, People's Republic of China. Electronic address: yucunliu@bjmu.edu.cn.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D004195:Disease Models, Animal; D017097:Electric Impedance; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020895:Enterocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C529376:GYY 4137; D005765:Gastrointestinal Agents; D008070:Lipopolysaccharides; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D020011:Protective Agents; D062725:Tight Junction Proteins; D014409:Tumor Necrosis Factor-alpha; C082161:lipopolysaccharide A; D007371:Interferon-gamma
keywords: GYY4137; Hydrogen sulfide; LPS; NF-kB; Tight junction