CD9 is critical for cutaneous wound healing through JNK signaling

J Invest Dermatol. 2012 Jan;132(1):226-36. doi: 10.1038/jid.2011.268. Epub 2011 Sep 1.

Abstract

Cutaneous injury triggers a cascade of signaling events essential for wound re-epithelialization. CD9, a cell-surface protein, has been implicated in a number of cellular processes by coupling to intracellular signaling; however, its exact role in wound healing remains unidentified. We reported that CD9 was downregulated in migrating epidermis, and reelevated to basal level when re-epithelialization was completed. Although low level of CD9 appears to be required for normal wound healing, a significant healing delay was found in CD9-null mice, with wounds gaping wider on day 5 and day 7 post wounding. Further analysis showed that re-epithelialization was adversely affected in CD9-null mice, due to impaired migration of epidermis. Notably, CD9 deficiency caused a persistent enhancement of C-JUN NH2 terminal kinase (JNK) signaling primarily in migrating epidermis with abnormal elevation of matrix metalloproteinase (MMP)-9 detected in CD9-null wounds, leading to excessive degradation of type IV collagen, and thus a defective basement membrane at the wound site. JNK suppression reduced MMP-9 production and therefore ameliorated the healing delay with the appearance of significantly elongated migrating epidermis in CD9-null mice. Our study demonstrated the importance of CD9 in wound re-epithelialization, linking this molecule directly to basement membrane formation and epidermal migration through participating in the regulation of the JNK/MMP-9 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane / metabolism
  • Cell Movement / physiology
  • Collagen Type IV / metabolism
  • Epidermis / injuries*
  • Epidermis / metabolism
  • Epidermis / physiology*
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Signal Transduction / physiology*
  • Tetraspanin 29 / metabolism
  • Tetraspanin 29 / physiology*
  • Wound Healing / physiology*

Substances

  • Cd9 protein, mouse
  • Collagen Type IV
  • Tetraspanin 29
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse