title: Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor.
abstract: Transforming growth factor beta (TGF-beta) and the platelet-derived growth factor (PDGF) are potent mitogenic polypeptides which enhance rates of wound healing in experimental animals; in contrast, glucocorticoids inhibit wound repair. The potential of TGF-beta and PDGF to reverse this inhibition in healing was tested in methylprednisolone-treated rats with deficits in skin wound strength of 50%. Single applications of TGF-beta (10-40 pmol per wound, 0.25-1 micrograms) applied locally at the time of wounding fully reversed this deficit in a concentration-dependent and highly reproducible manner. Wounds in glucocorticoid-treated animals were characterized by a near total absence of neutrophils and macrophages and by a delayed influx and reduced density of fibroblasts; however, such wounds treated with TGF-beta showed significant increases in wound fibroblasts and in intracellular procollagen type I. PDGF did not reverse the deficit in wound breaking strength in glucocorticoid-treated rats; there were more fibroblasts in the PDGF-treated wounds, but these fibroblasts lacked the enhanced expression of procollagen type I found in TGF-beta-treated wounds. The wound macrophages, required for normal tissue repair, remained absent from both PDGF- and TGF-beta-treated wounds in glucocorticoid-treated animals. This result suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of procollagen type I in fibroblasts. Whereas PDGF does not stimulate procollagen synthesis, in a rodent macrophage cell line, PDGF induced a highly significant, time-dependent enhancement of expression of TGF-beta.
authors.affiliation: Department of Pathology, Jewish Hospital, Washington University Medical Center, Saint Louis, MO 63110.
authors.forename: G F
authors.initials: GF
authors.lastname: Pierce
authors.forename: T A
authors.initials: TA
authors.lastname: Mustoe
authors.forename: J
authors.initials: J
authors.lastname: Lingelbach
authors.forename: V R
authors.initials: VR
authors.lastname: Masakowski
authors.forename: P
authors.initials: P
authors.lastname: Gramates
authors.forename: T F
authors.initials: TF
authors.lastname: Deuel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D051379:Mice; D008807:Mice, Inbred BALB C; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000235:genetics / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D000077555:Methylprednisolone Acetate; D015291:Transforming Growth Factors; D003094:Collagen; D008775:Methylprednisolone