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Dimerization of human pS2 (TFF1) plays a key role in its protective/healing effects
Author(s) -
Marchbank Tania,
Westley Bruce R.,
May Felicity E. B.,
Calnan Denis P.,
Playford Raymond J.
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199806)185:2<153::aid-path87>3.0.co;2-5
Subject(s) - wound healing , key (lock) , microbiology and biotechnology , biology , medicine , immunology , ecology
Human pS2 (trefoil factor family 1, TFF1), a 60‐amino acid member of the trefoil peptide family, forms dimers via Cys 58 and may stimulate gut repair. The effects of dimeric pS2‐TFF1 and monomeric pS2‐TFF1 (Cys 58 replaced by Ser 58 ) 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 Cys 58 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.