title: Activation of protease-activated receptor (PAR) 1 by frog trefoil factor (TFF) 2 and PAR4 by human TFF2.
abstract: Trefoil factors (TFFs) promote epithelial cell migration to reseal superficial wounds after mucosal injury, but their receptors and the molecular mechanisms underlying this process are poorly understood. In this study, we showed that frog TFF2 activates protease-activated receptor (PAR) 1 to induce human platelet aggregation. Based on this result, we further tested the involvement of PARs in human TFF2 (hTFF2)-promoted mucosal healing. hTFF2-stimulated migration of epithelial HT-29 cells was largely inhibited by PAR4 depletion with small interfering RNAs but not by PAR1 or PAR2 depletion. The PAR4-negative epithelial cell lines AGS and LoVo were highly responsive to hTFF2 as assessed by phosphorylation of ERK1/2 and cell migration upon PAR4 expression. Our findings suggest that hTFF2 promotes cell migration via PAR4. These findings will be helpful in further investigations into the functions and molecular mechanisms of TFFs and PARs in physiology and disease.
authors: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan, China.
authors: Yong
authors: Y
authors: Zhang
authors: Guoyu
authors: G
authors: Yu
authors: Yanjie
authors: Y
authors: Wang
authors: Yang
authors: Y
authors: Xiang
authors: Qian
authors: Q
authors: Gao
authors: Ping
authors: P
authors: Jiang
authors: Jie
authors: J
authors: Zhang
authors: Wenhui
authors: W
authors: Lee
authors: Yun
authors: Y
authors: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000071164:Trefoil Factor-2
chemical_list: D010455:Peptides; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; C112908:protease-activated receptor 4