title: Vasopressin regulation of epithelial colonic proliferation and permeability is mediated by pericryptal platelet-derived growth factor A.
abstract: Arginine vasopressin (AVP) has trophic effects on the rat distal colon, increasing the growth of pericryptal myofibroblasts and reducing the colonic crypt wall permeability. This study aimed to reproduce in vitro the effects of AVP observed in vivo using cultures of human CCD-18Co myofibroblasts and T84 colonic epithelial cells. Proliferation of myofibroblasts was quantified by bromodeoxyuridine incorporation; the expression of platelet-derived growth factor A (PDGFA), platelet-derived growth factor B, epidermal growth factor, transforming growth factor-β and vascular endothelial growth factor was measured by PCR and the expression of epithelial junction proteins by Western blot. Arginine vasopressin stimulated myofibroblast proliferation and the expression of PDGFA without affecting the expression of platelet-derived growth factor B, epidermal growth factor, transforming growth factor-β or vascular endothelial growth factor. These effects were prevented when AVP receptor inhibitors were present in the medium. Pre-incubation of CCD-18Co cells with anti-PDGF antibody or with an inhibitor of the PDGF receptor abolished the effects of AVP. When colonocytes were incubated with medium obtained from myofibroblasts incubated with AVP, both cell proliferation and the expression of epithelial junction proteins increased; however, direct incubation of colonocytes with AVP did not modify these variables. These results demonstrate that AVP stimulates myofibroblast proliferation and induces PDGFA secretion, implying that PDGFA mediates local myofibroblast proliferation by an autocrine feedback loop and regulates epithelial proliferation and permeability by a paracrine mechanism.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona (UB), Barcelona, Spain lluisa.miro@ub.edu.
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Miró
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Pérez-Bosque
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Maijó
authors.affiliation: Physiology Department, King's College London, London, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Naftalin
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Moretó
mesh_terms: D001127:Arginine Vasopressin / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010539:Permeability; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D001127:Arginine Vasopressin