title: 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: Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of Ministry of Education of China, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors: Jiaping
authors: J
authors: Zhang
authors: Jianda
authors: J
authors: Dong
authors: Hua
authors: H
authors: Gu
authors: Sidney
authors: S
authors: Yu
authors: Xiaohu
authors: X
authors: Zhang
authors: Yulin
authors: Y
authors: Gou
authors: Wenming
authors: W
authors: Xu
authors: Andrew
authors: A
authors: Burd
authors: Lin
authors: L
authors: Huang
authors: Kenji
authors: K
authors: Miyado
authors: Yuesheng
authors: Y
authors: Huang
authors: Hsiao Chang
authors: HC
authors: Chan
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D004817:Epidermis / Q000293:injuries* / Q000378:metabolism / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000502:physiology*; D060245:Tetraspanin 29 / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: C554870:Cd9 protein, mouse; D024141:Collagen Type IV; D060245:Tetraspanin 29; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse