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

Noriko Aramaki, Satsuki Mochizuki, Kazuo Kishi, Tatsuo Nakajima, Hironari Takaishi, Jeanine D'Armiento, Yasunori Okada

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Abstract

Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wildtype mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MMP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-β1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration.

Original languageEnglish
Pages (from-to)533-546
Number of pages14
JournalAmerican Journal of Pathology
Volume175
Issue number2
DOIs
Publication statusPublished - 2009 Aug

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Matrix Metalloproteinase 13
Keratinocytes
Wound Healing
Matrix Metalloproteinase 9
Skin
Knockout Mice
Wounds and Injuries
Myofibroblasts
Fibroblasts
Re-Epithelialization
Connective Tissue Growth Factor
Matrix Metalloproteinase Inhibitors
Transforming Growth Factors
Matrix Metalloproteinases

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. / Aramaki, Noriko; Mochizuki, Satsuki; Kishi, Kazuo; Nakajima, Tatsuo; Takaishi, Hironari; D'Armiento, Jeanine; Okada, Yasunori.

In: American Journal of Pathology, Vol. 175, No. 2, 08.2009, p. 533-546.

Research output: Contribution to journalArticle

Aramaki, Noriko ; Mochizuki, Satsuki ; Kishi, Kazuo ; Nakajima, Tatsuo ; Takaishi, Hironari ; D'Armiento, Jeanine ; Okada, Yasunori. / MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. In: American Journal of Pathology. 2009 ; Vol. 175, No. 2. pp. 533-546.
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