title: Recombinant human platelet-derived growth factor enhanced dermal wound healing by a pathway involving ERK and c-fos in diabetic rats.
abstract: BACKGROUND
  Platelet-derived growth factor (PDGF) has been shown to promote dermal wound healing, however, the molecular mechanisms responsible for are not fully understood.
  
  
  OBJECTIVE
  The present study was undertaken to investigate the possible signaling mechanisms by which PDGF improved healing of cutaneous wound in diabetic rats.
  
  
  METHODS
  Four full-thickness skin wounds were created on the dorsum of Wistar diabetic rats. Animals were treated with or without recombinant human PDGF (rhPDGF) at 7.0 microg/cm(2) wound or vehicle daily 1 day after wounding. The animals were then killed after various intervals of wounding, and the wounded skin tissues were used for histological evaluation, analysis of the phosphorylation of extracellular signal-regulated kinases (ERK) and the expression of c-fos protein, as well as the labeling indices of proliferative cell nuclear antigen (PCNA).
  
  
  RESULTS
  Topical application of rhPDGF significantly accelerated the rate of reepithelialization compared with vehicle-treated or untreated group at 7 days after wounding. At the histological level, the significant increases in the degree of reepithelialization, the thickness of granulation tissue and the density of capillary bud were observed in the wound sites in rhPDGF-treated group at 7 and 14 days after wounding. Moreover, treatment with rhPDGF increased PCNA labeling indices, c-fos protein expression and ERK phosphorylation in the wounded tissues at the indicated time after wounding.
  
  
  CONCLUSIONS
  These results suggest that application of rhPDGF increases cell proliferation, and enhances dermal tissue repair in diabetic skin lesion of rats, which might be partly mediated by ERK activation and c-fos protein expression.
authors.affiliation: Department of Plastic Surgery, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, Guangdong Province 510010, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Liu
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Fu
authors.forename: Tong-Zhu
authors.initials: TZ
authors.lastname: Sun
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D001786:Blood Glucose / Q000378:metabolism; D020405:Dermis / Q000293:injuries*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D001786:Blood Glucose; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D048049:Extracellular Signal-Regulated MAP Kinases