Hepatocyte growth factor regulation: an integral part of why wounds become chronic.
Hepatocyte growth factor (HGF) is a cytokine known to play multiple roles during the various stages of wound healing. This study addresses the ongoing key questions regarding the role of HGF in wound healing, namely: are HGF and its regulators expressed differently in chronic and acute wounds? Biopsies from normal skin (n=10), acute (n=10), and chronic wounds (n=17) were analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR for the presence of HGF, its receptor cMet, its activators and its inhibitors. Immunohistochemical staining for HGF, HGF activators, and HGF inhibitors was similar, with expression being greater in chronic wound dermis compared with acute wound dermis. While expression of cMet in chronic wound dermis was less than in the acute wound dermis. PCR quantification of these proteins showed similar trends although the differences did not reach statistical significance. The results of this study provide important data confirming the role of HGF in wound healing. In addition, we have demonstrated the aberrant expression of the HGF receptor cMet and activation inhibitors (HAI-1 and HAI-2) in chronic wounds. This aberrant expression may have a value in predicting the process of healing and nonhealing wounds and constitute important targets of future therapies.
Conway
Kevin
K
Wound Healing Research Unit, Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom. kevinconway@doctors.org.uk
Ruge
Fiona
F
Price
Patricia
P
Harding
Keith G
KG
Jiang
Wen G
WG
D000208:Acute Disease; D002908:Chronic Disease; D020405:Dermis / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000378:metabolism / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000503:physiopathology*
D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; C109148:SPINT2 protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D012697:Serine Endopeptidases; C485595:matriptase