Marchbank T, Westley B R, May F E, Calnan D P, Playford R J
University Division of Gastroenterology, Leicester General Hospital, U.K.
J Pathol. 1998 Jun;185(2):153-8. doi: 10.1002/(SICI)1096-9896(199806)185:2<153::AID-PATH87>3.0.CO;2-5.
Human pS2 (trefoil factor family 1, TFF1), a 60-amino acid member of the trefoil peptide family, forms dimers via Cys58 and may stimulate gut repair. The effects of dimeric pS2-TFF1 and monomeric pS2-TFF1 (Cys58 replaced by Ser58) were compared in models of wound healing. Rats given dimeric pS2-TFF1 at 25 and 50 micrograms/kg per h had 50 per cent and 70 per cent reduction in gastric damage induced respectively by indomethacin (20 mg/kg subcutaneously) and restraint (P < 0.01). Monomeric pS2-TFF1, at the same doses, was significantly less effective at reducing injury (about half the amount of protection, P < 0.01 vs. same doses of dimeric). The rate of migration of cells at the leading edge of wounded monolayers of the human colonic cell line HT29 was increased by addition of dimeric or monomeric forms of pS2-TFF1 (0.65-325 micrograms/ml). Dimeric pS2-TFF1 had a greater effect than the monomeric form at all doses tested (P < 0.05). Cell migration induced by pS2-TFF1 was blocked by a pS2-TFF1 antibody, but not by a transforming growth factor beta neutralizing antibody. pS2-TFF1 did not influence cell proliferation as assessed by thymidine incorporation. The increased biological effects of dimeric pS2-TFF1 might be due to direct interaction of Cys58 with a putative trefoil receptor or, more likely, dimerization of pS2-TFF1 might stabilize the interaction with its receptor. This may involve a bivalent interaction of residues on the surfaces of the two trefoil domains.
人pS2（三叶因子家族1，TFF1）是三叶肽家族中一个由60个氨基酸组成的成员，通过半胱氨酸58形成二聚体，可能刺激肠道修复。在伤口愈合模型中比较了二聚体pS2-TFF1和单体pS2-TFF1（半胱氨酸58被丝氨酸58取代）的作用。每小时给予大鼠25微克/千克和50微克/千克二聚体pS2-TFF1，分别使吲哚美辛（20毫克/千克皮下注射）和束缚诱导的胃损伤减少50%和70%（P<0.01）。相同剂量的单体pS2-TFF1在减轻损伤方面效果明显较差（保护量约为二聚体的一半，与相同剂量的二聚体相比P<0.01）。添加二聚体或单体形式的pS2-TFF1（0.65 - 325微克/毫升）可增加人结肠细胞系HT29受伤单层前沿细胞的迁移率。在所有测试剂量下，二聚体pS2-TFF1的作用均大于单体形式（P<0.05）。pS2-TFF1诱导的细胞迁移被pS2-TFF1抗体阻断，但不被转化生长因子β中和抗体阻断。通过胸苷掺入评估，pS2-TFF1不影响细胞增殖。二聚体pS2-TFF1生物学效应增强可能是由于半胱氨酸58与假定的三叶因子受体直接相互作用，或者更有可能的是，pS2-TFF1二聚化可能稳定其与受体的相互作用。这可能涉及两个三叶结构域表面残基的二价相互作用。
