CD9 is critical for cutaneous wound healing through JNK signaling.

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.

• Authors: Jiaping Zhang, Jianda Dong, Hua Gu, Sidney Yu, Xiaohu Zhang, Yulin Gou, Wenming Xu, Andrew Burd, Lin Huang, Kenji Miyado, Yuesheng Huang, Hsiao Chang Chan
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 132 Issue 1 Pg. 226-36 (Jan 2012) ISSN: 1523-1747 [Electronic] United States
• PMID: 21881583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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