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.
J Invest Dermatol. 2012 Jan;132(1):226-36. doi: 10.1038/jid.2011.268. Epub 2011 Sep 1.
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.
皮肤损伤会引发一系列对伤口再上皮化至关重要的信号事件。CD9 是一种细胞表面蛋白，通过与细胞内信号偶联，参与了许多细胞过程；然而，其在伤口愈合中的确切作用仍未确定。我们报道 CD9 在迁移的表皮中下调，当再上皮化完成时，重新升高到基底水平。虽然低水平的 CD9 似乎是正常伤口愈合所必需的，但在 CD9 缺失的小鼠中发现了明显的愈合延迟，伤口在第 5 天和第 7 天愈合时张开得更大。进一步的分析表明，由于表皮迁移受损，CD9 缺失的小鼠再上皮化受到不利影响。值得注意的是，CD9 缺乏导致 C-JUN NH2 末端激酶 (JNK) 信号持续增强，主要在迁移的表皮中，在 CD9 缺失的伤口中检测到基质金属蛋白酶 (MMP)-9 的异常升高，导致 IV 型胶原过度降解，从而在伤口部位形成有缺陷的基底膜。JNK 抑制减少了 MMP-9 的产生，从而改善了愈合延迟，CD9 缺失的小鼠中出现了明显延长的迁移表皮。我们的研究表明 CD9 在伤口再上皮化中的重要性，通过参与 JNK/MMP-9 通路的调节，将该分子直接与基底膜形成和表皮迁移联系起来。
