MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing

Related Experiment Video

Updated: Jun 21, 2026

Scratch Migration Assay and Dorsal Skinfold Chamber for In Vitro and In Vivo Analysis of Wound Healing
09:34

Scratch Migration Assay and Dorsal Skinfold Chamber for In Vitro and In Vivo Analysis of Wound Healing

Published on: September 26, 2019

Noriko Hattori1, Satsuki Mochizuki, Kazuo Kishi

  • 1Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.

The American Journal of Pathology
|July 11, 2009
PubMed

Insights

Matrix metalloproteinases (MMPs), specifically MMP-9 and MMP-13, are crucial for effective wound healing. Their absence in knockout mice significantly delayed wound closure, re-epithelialization, and contraction, highlighting their essential roles.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Wound Healing Research

Background:

  • Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix remodeling.
  • MMPs have been suggested to play a role in the complex process of wound healing.
  • The specific contributions of MMP-9 and MMP-13 to cutaneous wound repair remain to be fully elucidated.

Purpose of the Study:

  • To investigate the distinct and overlapping roles of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-13 (MMP-13) in cutaneous wound healing.
  • To analyze the impact of MMP-9 and MMP-13 deficiency on key stages of the wound healing process, including re-epithelialization, angiogenesis, and contraction.

Main Methods:

  • Generation of full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wild-type (WT) mice.
  • Macroscopic assessment of wound closure rates and histological analysis of re-epithelialization and vascularization.
  • In vitro studies using keratinocyte migration assays and fibroblast differentiation models, with and without MMP inhibition or gene silencing.

Main Results:

  • All MMP knockout mouse models exhibited delayed macroscopic wound closure compared to WT mice.
  • Re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice, and remarkably so in double KO mice.
  • MMP-13 deficiency led to reduced angiogenesis and impaired wound contraction, alongside decreased myofibroblast formation and differentiation.
  • Both MMP-9 and MMP-13 were expressed at the leading edge of migrating epidermal cells, and their inhibition suppressed keratinocyte migration.

Conclusions:

  • MMP-13 plays a critical role in keratinocyte migration, angiogenesis, and wound contraction during the healing process.
  • MMP-9 primarily contributes to keratinocyte migration in wound repair.
  • Combined deficiency of MMP-9 and MMP-13 severely impairs multiple aspects of cutaneous wound healing.

More Related Videos

Zebrafish Keratocyte Explants to Study Collective Cell Migration and Reepithelialization in Cutaneous Wound Healing09:35

Zebrafish Keratocyte Explants to Study Collective Cell Migration and Reepithelialization in Cutaneous Wound Healing

Published on: February 25, 2015

Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.09:06

Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.

Published on: March 25, 2020

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Phases of Wound Repair01:28

Phases of Wound Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...
Renewal of Skin Epidermal Stem Cells01:12

Renewal of Skin Epidermal Stem Cells

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
The Extracellular Matrix01:42

The Extracellular Matrix

In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.Composition of the Extracellular MatrixThe extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse molecules.