Cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require distinct structure basis.
Human trefoil factors (TFFs) play an important role in wound healing, epithelial restitution and anti-inflammatory effects in the gastrointestinal tract by stimulating cell migration and inhibiting cell apoptosis. In our previous study, Bm-TFF2, an amphibian trefoil factor, which is isolated from the skin secretions of frog Bombina maxima, has much stronger activities than human TFFs. We believe that the expression of the recombinant Bm-TFF2 in vitro is useful to decipher its role in amphibian skin repair. Bm-TFF2 contains 12 cysteine residues and has two TFF-domains. In this study, we expressed full-length of Bm-TFF2 and its single-domain truncations (Bm-TFF2-D1 and Bm-TFF2-D2, each contains a single TFF-domain of Bm-TFF2). The recombinant proteins, including full-length and its single-domain truncations of Bm-TFF2, can promote the migration of human epithelial AGS cells and wound healing of rat intestinal epithelial IEC-6 cells. However, only the full-length of Bm-TFF2, but not its single-domain truncations, can inhibit ceramide-induced apoptosis in AGS cells. In summary, it is the first time to use the recombinant Bm-TFF2 and its truncations to investigate its structure-function relationship. And we report that full-length and each domain of Bm-TFF2 can induce cell migration but only the full-length of Bm-TFF2 can suppress apoptosis, indicating that cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require distinct structure basis.
Yu
Guoyu
G
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.
Zhang
Yong
Y
Xiang
Yang
Y
Jiang
Ping
P
Chen
Zhongming
Z
Lee
Wenhui
W
Zhang
Yun
Y
D000818:Animals; D001001:Anura; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics; D012038:Regeneration; D012879:Skin Physiological Phenomena; D000071164:Trefoil Factor-2; D014945:Wound Healing
D010455:Peptides; D011994:Recombinant Proteins; C000604007:TFF2 protein, human; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3