CD9 is critical for cutaneous wound healing through JNK signaling.
CD9 is critical for cutaneous wound healing through JNK signaling.
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DOI：
10.1038/jid.2011.268
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Jiaping Zhang;J. Dong;Hua Gu;Sidney Siu Bun Yu;Xiaohu Zhang;Y. Gou;W. Xu;A. Burd;Lin Huang-Lin
中科院分区：
文献类型：
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作者：
Jiaping Zhang;J. Dong;Hua Gu;Sidney Siu Bun Yu;Xiaohu Zhang;Y. Gou;W. Xu;A. Burd;Lin Huang-Lin
皮肤损伤触发了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，通过与细胞内信号的偶联参与了许多细胞过程；然而，它在伤口愈合中的确切作用尚不清楚。我们报道了CD9在迁移中的表皮中表达下调，并在重新上皮化完成后恢复到基础水平。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显著的愈合延迟，创伤后第5天和第7天伤口张开得更大。进一步的分析表明，由于表皮迁移受阻，CD9基因缺失的小鼠的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)信号的持续增强，主要发生在迁移的表皮中，在CD9缺失的创面中检测到基质金属蛋白酶(MMP)-9的异常升高，导致IV型胶原的过度降解，从而导致创面基底膜的缺陷。抑制JNK减少了基质金属蛋白酶-9的产生，因此改善了愈合延迟，在CD9缺失的小鼠中出现了显着延长的移行表皮。我们的研究证实了CD9在创面再上皮化中的重要性，通过参与JNK/MMP9通路的调节，将CD9分子直接连接到基底膜的形成和表皮的迁移。
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.