title: Improvement of the breaking strength of wound by combined treatment with recombinant human G-CSF, recombinant human M-CSF, and a TGF-beta1 receptor kinase inhibitor in rat skin.
abstract: Effective doses of ionizing radiation during preoperative radiotherapy occasionally cause wound complications after subsequent surgery. The authors attempted to accelerate radiation-impaired wound healing in animal models. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human macrophage colony-stimulating factor (rhM-CSF), and an inhibitor of transforming growth factor (TGF)-beta1 receptor kinase, SB431542, were injected s.c. into a full-thickness incisional wound site in the dorsal skin of rats after local irradiation of X-ray (30 Gy). Wound healing of irradiated skin was assessed using the breaking strength of the wound and histological analyses. The impaired wound healing in irradiated skin was found to be associated with impaired mobilization of bone marrow-derived cells and enhanced expression of TGF-beta1 mRNA. The breaking strength of the wound in the irradiated skin was approximately one-eighth of that in the non-irradiated skin; however, following combined treatment with the above three compounds the breaking strength increased to approximately one-half of that in the non-irradiated skin. Histological analysis of the wounded skin revealed an increase in formation of collagen fibers and the panniculus carnosus following the combined treatment. Moreover, the increased breaking strength was associated with an increase in a subpopulation of fibrocytes (collagen I/ED1 double positive cells). These findings suggested that a combined treatment with rhG-CSF, rhM-CSF, and SB431542 is promising as a means of improving radiation-impaired wound healing.
authors.affiliation: Experimental Animal Laboratory, Research Center for Innovative Oncology, Chiba, Japan. ksugiyam@east.ncc.go.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
mesh_terms: D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D016038:Skin Transplantation; D013718:Tensile Strength; D014945:Wound Healing
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D003115:Colony-Stimulating Factors; D004149:Dioxoles; D004791:Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat