Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

Exp Dermatol. 2010 Aug;19(8):e234-40. doi: 10.1111/j.1600-0625.2009.01062.x.

Abstract

During healing of incisional skin wounds, migrating keratinocytes dissect their way under the crust to re-epithelialize the wounded area. The efficiency of this tissue remodelling process depends on the concomitant activity of several extracellular proteases, including members of the plasminogen activation (PA) system and the matrix metalloproteinase (MMP) family. Treatment with the broad spectrum MMP inhibitor, galardin, delays wound healing in wildtype mice and completely arrest wound healing in plasminogen (Plg)-deficient mice, indicating a functional overlap between plasmin- and galardin-sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing was not significantly different between Plg-deficient and MMP2/Plg double-deficient mice. These results show that MMP2 activity is not essential for wound healing and indicate that lack of MMP2 only marginally potentiates the effect of Plg deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dipeptides / pharmacology
  • Matrix Metalloproteinase 2 / deficiency*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Models, Animal
  • Plasminogen / deficiency*
  • Plasminogen / genetics
  • Plasminogen / metabolism
  • Protease Inhibitors / pharmacology
  • RNA, Messenger / metabolism
  • Skin / injuries*
  • Skin / metabolism
  • Wound Healing / physiology*

Substances

  • Dipeptides
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Protease Inhibitors
  • RNA, Messenger
  • Plasminogen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9