Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them

Trung T. Nguyen, William R. Wolter, Bowen Anderson, Valerie A. Schroeder, Ming Gao, Major Gooyit, Mark A. Suckow, Mayland Chang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalACS Pharmacology and Translational Science
Volume3
Issue number3
DOIs
StatePublished - Jun 12 2020

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.

Keywords

  • MMP-13
  • MMP-2
  • MMP-8
  • MMP-knockout
  • diabetic mice
  • wound healing

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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