Topical Application of Tat-Rac1 Promotes Cutaneous Wound Healing in Normal and Diabetic Mice.
Topical Application of Tat-Rac1 Promotes Cutaneous Wound Healing in Normal and Diabetic Mice.
复制标题
局部应用 Tat-Rac1 可促进正常和糖尿病小鼠的皮肤伤口愈合。
DOI：
10.7150/ijbs.25920
复制
发表时间：
2018
影响因子：
9.2
通讯作者：
Wang XJ
中科院分区：
文献类型：
--
作者：
Fan B;Wang T;Bian L;Jian Z;Wang DD;Li F;Wu F;Bai T;Zhang G;Muller N;Holwerda B;Han G;Wang XJ
内源性小GTdR，Rac 1，在正常皮肤伤口愈合过程中起着关键作用。内源性Rac 1是否能在慢性伤口中被适当激活仍有待确定;如果不能，外源性Rac 1是否对伤口愈合具有治疗作用。在这里，我们表明，在愈合过程中，db/db糖尿病小鼠的伤口中Rac 1蛋白水平低于野生型小鼠的伤口。为了评估外源性Rac 1在伤口愈合中的治疗潜力，我们产生了通过蛋白转导进入细胞的Tat-Rac 1融合蛋白。Tat-Rac 1在体外增加角质形成细胞和真皮成纤维细胞的增殖和迁移。局部应用Tat-Rac 1加速db/db小鼠以及野生型小鼠体内皮肤伤口闭合。进一步的分析显示，与媒介物处理的伤口相比，Tat-Rac 1具有更快的再上皮化、更高的角质形成细胞增殖和迁移，而没有更早的肌成纤维细胞活化。Tat-Rac 1还减少了伤口的炎症。我们的研究结果揭示了糖尿病伤口未能提高Rac 1表达，并建议使用基于Rac 1的生物制剂来弥补这一缺陷，从而促进伤口愈合。
The endogenous small GTPase, Rac1, plays a critical role during normal skin wound healing. It remains to be determined whether endogenous Rac1 can be appropriately activated in chronic wounds; if not, whether exogenous Rac1 has therapeutic effects on wound healing. Here we show that Rac1 protein levels were lower in wounds of db/db diabetic mice than wounds in wild type mice during the healing process. To assess the therapeutic potential of exogenous Rac1 in wound healing, we produced a Tat-Rac1 fusion protein that enters into cells through protein transduction. Tat-Rac1 increased proliferation and migration of keratinocytes and dermal fibroblasts in vitro. Topical application of Tat-Rac1 accelerated cutaneous wound closure in vivo in db/db mice as well as wild type mice. Further analyses revealed that Tat-Rac1 had faster re-epithelialization, higher keratinocyte proliferation and migration without an earlier onset of myofibroblast activation than vehicle treated wounds. Tat-Rac1 also reduced inflammation in wounds. Our findings revealed the failure of diabetic wounds to elevate Rac1 expression and suggested a therapeutic strategy utilizing a Rac1-based biologic to compensate for this defect thereby promoting wound healing.
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DOI：
10.1016/j.jid.2017.08.043
发表时间：
2018-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Bhatia A;O'Brien K;Guo J;Lincoln V;Kajiwara C;Chen M;Woodley DT;Udono H;Li W
通讯作者：
Li W
影响因子：
6
作者：
Han, Gangwen;Li, Fulun;Wang, Xiao-Jing
通讯作者：
Wang, Xiao-Jing
影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
3.7
作者：
Castilho RM;Squarize CH;Leelahavanichkul K;Zheng Y;Bugge T;Gutkind JS
通讯作者：
Gutkind JS
影响因子：
15.9
作者：
Winge, Marten C. C.;Ohyama, Bungo;Marinkovich, M. Peter
通讯作者：
Marinkovich, M. Peter