title: Bm-TFF2, a toad trefoil factor, promotes cell migration, survival and wound healing.
abstract: Toad skin is naked and continually confronted by various injurious factors. Constant skin renewal and repairs occur frequently. However, the mechanisms of the renewal and repair have not clearly elucidated. In our previous work, a trefoil factor (TFF), Bm-TFF2, has been purified from the Bombina maxima skin and characterized as a platelet agonist. The mRNA of TFFs in toad skin was up-regulated greatly during the metamorphosis, indicating a pivotal role of TFFs in amphibian skin. Here, we presented the effects of Bm-TFF2 on the cell migration, apoptosis and proliferation. Bm-TFF2 bound to epithelial cells and showed strong cell motility activity. At the concentrations of 1-100nM, Bm-TFF2-induced migration of human epithelial AGS and HT-29 cells, and rat intestinal epithelial IEC-6 cell lines. The in vitro wound healing assay also verified the activity of Bm-TFF2. Bm-TFF2 could also inhibit cell apoptosis induced by ceramide and sodium butyrate. The cell migration-promoting activity was abolished by MEK1 inhibitors, U0126 and PD98059, suggesting that ERK1/2 activation is crucial for Bm-TFF2 to stimulate cell migration. Taken together, Bm-TFF2 promoted wound healing by stimulating cell migration via MAPK pathway and preventing cell apoptosis. The potent biological activity of Bm-TFF2 makes it a useful molecular tool for further studies of structure-function relationship of the related human TFFs.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guoyu
authors.initials: G
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lee
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015539:Platelet Activation; D051381:Rats; D012867:Skin / Q000737:chemistry; D000071164:Trefoil Factor-2; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010455:Peptides; C000604007:TFF2 protein, human; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D020929:Mitogen-Activated Protein Kinase Kinases