Cell and Tissue Research

, Volume 306, Issue 2, pp 239–250

Hepatocyte growth factor and macrophage-stimulating protein are upregulated during excisional wound repair in rats

  • Allison J. Cowin
  • Nick Kallincos
  • Nick Hatzirodos
  • Gray J. Robertson
  • Kaylene J. Pickering
  • Jenny Couper
  • David A. Belford
Regular Article

DOI: 10.1007/s004410100443

Cite this article as:
Cowin, A.J., Kallincos, N., Hatzirodos, N. et al. Cell Tissue Res (2001) 306: 239. doi:10.1007/s004410100443

Abstract.

Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) are structurally related molecules that stimulate epithelial cell proliferation and migration. MSP also acts directly as a chemoattractant for resident macrophages. These activities are integral to the wound repair processes of inflammation, epithelialization and tissue remodelling. To begin to examine the involvement of HGF and MSP in healing of cutaneous wounds we have mapped the temporal expression of these two molecules and their receptors, MET and RON respectively, in adult rat excisional wounds. Four 2×2-cm full-thickness excisional wounds were created on the dorsum of 18 rats, and biopsies were taken through the wounds at 3, 5, 7, 14, 21, and 28 days postwounding. These biopsies were analyzed using immunofluorescent staining and in situ hybridization (ISH). The number of cells staining positively for HGF and MET significantly increased in response to wounding. HGF staining and mRNA peaked at 7 days postwounding whereas MET was upregulated earlier, peaking after 3 days. Both HGF and MET protein were observed in fibroblasts of the dermis and in the newly forming granulation tissue. ISH studies also revealed that fibroblasts at the wound edges and within the newly forming granulation tissue also expressed HGF and c-met mRNA. Immunofluorescent staining revealed both MSP and RON within the wound, with maximum staining occurring between 7 and 21 days for both the ligand and receptor. In addition, MSP co-localized with a small subset of ED1-positive cells (monocytes). In contrast, ED2-positive cells (macrophages) did not co-localize with MSP. Thus, increased expression of HGF, MSP and their receptors MET and RON respectively was observed in response to wounding. Furthermore, MSP co-localization with a subset of monocytes may confirm a role for MSP in the activation of mature macrophages, which may be important in tissue remodelling.

HGF MET MSP RON Inflammation Wound healing Rat (Sprague Dawley)

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Allison J. Cowin
    • 1
  • Nick Kallincos
    • 2
  • Nick Hatzirodos
    • 1
  • Gray J. Robertson
    • 1
  • Kaylene J. Pickering
    • 1
  • Jenny Couper
    • 2
  • David A. Belford
    • 1
  1. 1.Child Health Research Institute and CRC for Tissue Growth and Repair, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006, Australia
  2. 2.Department of Paediatrics, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006, Australia