Rac1 is required for epithelial stem cell function during dermal and oral mucosal wound healing but not for tissue homeostasis in mice.
Rac1 is required for epithelial stem cell function during dermal and oral mucosal wound healing but not for tissue homeostasis in mice.
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DOI：
10.1371/journal.pone.0010503
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发表时间：
2010-05-06
期刊：
影响因子：
3.7
通讯作者：
Gutkind JS
中科院分区：
文献类型：
--
作者：
Castilho RM;Squarize CH;Leelahavanichkul K;Zheng Y;Bugge T;Gutkind JS
皮肤的再生能力，包括脱落细胞的不断更换和损伤的愈合，依赖于表皮干细胞及其直接细胞后代。毛囊干细胞和毛囊间干细胞对皮肤创伤愈合的相对贡献是一个积极的研究领域。最近的研究表明，调节细胞迁移和核基因表达的小GTPase Rac 1是毛囊干功能所需的，但不是毛囊间皮肤正常稳态所需的。在这里，我们探讨了Rac 1是否有助于皮肤和口腔粘膜中的伤口愈合，口腔粘膜是一个解剖部位，其结构与皮肤相似，但缺乏任何毛囊结构，因此缺乏毛囊干细胞。表皮Rac1基因切除导致皮肤伤口明显延迟闭合。值得注意的是，从口腔粘膜中去除Rac 1基因导致口腔伤口完全无法愈合。我们目前的证据表明，缺乏口腔粘膜再上皮化可能是由于缺乏Rac1的细胞迁移能力降低，以及损伤诱导的增殖和细胞应激相关的表达程序的表达改变。总之，这些观察结果支持，虽然正常发育和稳态的毛囊间皮肤和口腔粘膜不需要Rac 1功能，毛囊间和口腔上皮干细胞可能需要Rac 1依赖的程序来协调组织对损伤的反应，并最终用于伤口闭合。最终，这些发现可能使这些干细胞群的急性组织再生反应的分子表征，从而促进旨在加速伤口闭合的新型分子靶向策略的鉴定。
The regenerative capacity of the skin, including the continuous replacement of exfoliated cells and healing of injuries relies on the epidermal stem cells and their immediate cell descendants. The relative contribution of the hair follicle stem cells and the interfollicular stem cells to dermal wound healing is an area of active investigation. Recent studies have revealed that the small GTPase Rac1, which regulates cell migration and nuclear gene expression, is required for hair follicle stem function but not for the normal homeostasis of the interfollicular skin. Here we explored whether Rac1 contributes to wound healing in the skin and in the oral mucosa, the latter an anatomical site that presents similar architecture to that of the skin but is devoid of any hair follicle structures, and hence lacks hair follicle stem cells. Epidermal Rac1 gene excision led to the clearly delayed closure of cutaneous wounds. Remarkably, genetic ablation of Rac1 from the oral mucosa resulted in the complete inability of oral wounds to heal. We present evidence that the lack of oral mucosal re-epithelization may result from the reduced migratory capacity of cells lacking Rac1 together with altered expression of injury-induced proliferative and cellular stress-related expression programs. Together, these observations support that while the normal development and homeostasis of the interfollicular skin and oral mucosa do not require Rac1 function, the interfollicular and oral epithelial stem cells may require a Rac1-dependent program to orchestrate the tissue response to injury and ultimate for wound closure. Ultimately, these findings may enable the molecular characterization of the acute tissue regenerative response of these stem cell populations, thus facilitating the identification of novel molecular-targeted strategies aimed at accelerating wound closure.
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影响因子：
3.3
作者：
Braga, VMM;Betson, M;Lamarche-Vane, N
通讯作者：
Lamarche-Vane, N
影响因子：
46.9
作者：
Morris, RJ;Liu, YP;Cotsarelis, G
通讯作者：
Cotsarelis, G
影响因子：
23.9
作者：
Fuchs E
通讯作者：
Fuchs E
影响因子：
56.9
作者：
Gu, Y;Filippi, MD;Williams, DA
通讯作者：
Williams, DA
DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B