title: Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.
abstract: Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Zhaorui
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Danbing
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Baodi
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, P.R. China.
authors.forename: Shinan
authors.initials: S
authors.lastname: Nie
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects*; D009025:Morpholines / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071164:Trefoil Factor-2
chemical_list: D002867:Chromones; D008070:Lipopolysaccharides; D009025:Morpholines; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000071164:Trefoil Factor-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one