Dimerization of human pS2 (TFF1) plays a key role in its protective/healing effects
Dimerization of human pS2 (TFF1) plays a key role in its protective/healing effects
复制标题
人 pS2 (TFF1) 的二聚化在其保护/治疗作用中发挥着关键作用
作者：
T. Marchbank;B. Westley;F. May;D. Calnan;R. Playford
人pS2（三叶因子家族1，TFF 1），三叶肽家族的60个氨基酸成员，通过Cys 58形成二聚体，并可能刺激肠道修复。在伤口愈合模型中比较了二聚体pS2-TFF 1和单体pS2-TFF 1（Cys 58被Ser 58替代）的作用。以25和50 μg/kg/h的剂量给予大鼠pS2-TFF 1二聚体，吲哚美辛（皮下注射20 mg/kg）和束缚诱导的胃损伤分别减少50%和70%（P<0.01）。在相同剂量下，单体pS2-TFF 1在减少损伤方面的有效性显著降低（约为保护量的一半，P<0.01，与相同剂量的二聚体相比）。通过加入二聚体或单体形式的pS2-TFF 1（0·65-325 μg/ml），人结肠细胞系HT 29损伤单层前缘的细胞迁移速率增加。在所有测试剂量下，二聚体pS2-TFF 1的作用大于单体形式（P<0.05）。pS2-TFF 1诱导的细胞迁移被pS2-TFF 1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-TFF 1不影响细胞增殖。二聚体pS2-TFF 1的生物学效应增加可能是由于Cys 58与推定的三叶受体直接相互作用，或者更可能的是，pS2-TFF 1的二聚体可能稳定与其受体的相互作用。这可能涉及两个三叶结构域表面上残基的二价相互作用。© 1998 John Wiley & Sons，Ltd。
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 μg/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 μg/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 β 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. © 1998 John Wiley & Sons, Ltd.
影响因子：
29.4
作者：
DIGNASS, AU;PODOLSKY, DK
通讯作者：
PODOLSKY, DK
影响因子：
29.4
作者：
Babyatsky, MW;deBeaumont, M;Podolsky, DK
通讯作者：
Podolsky, DK
影响因子：
15.9
作者：
DIGNASS, A;LYNCHDEVANEY, K;PODOLSKY, DK
通讯作者：
PODOLSKY, DK