CD271 promotes STZ-induced diabetic wound healing and regulates epidermal stem cell survival in the presence of the pTrkA receptor
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Diabetes mellitus (DM) often causes delayed wound healing in patients, which can lead to limb loss, disability, and even death. Many conventional therapeutic strategies have been proposed, but there is still no effective therapy for DM wounds. This study aimed to explore the effects of CD271 and phosphorylated tyrosine kinase receptor A (pTrkA) on the migration and proliferation abilities of epidermal stem cells (eSCs) and on the activation of DM wound healing. We investigated the interventional effects of CD271-overexpressing eSC (CD271 eSC) treatment and pTrkA inhibition (through k252a treatment) on delayed wound healing using mice with streptozotocin-induced DM. The migration and proliferation abilities of control eSCs, CD271 eSCs, and k252a-treated CD271 eSCs were observed under high-glucose conditions. Decreases in CD271 and increases in pTrkA were observed in DM mouse skin compared with control mouse skin; in addition, the rate of wound closure in DM mice was promoted by CD271 eSC treatment but delayed by pTrkA inhibition. Furthermore, the CD271 eSC migration and proliferation were greater than of control eSCs. Compared with that of CD271 eSCs, the number of CD271+k252a eSCs decreased significantly under high-glucose conditions. In parallel, the expression levels of the pERK, pAkt, and pJNK pathways increased in CD271 eSCs and decreased in CD271+k252a eSCs under high glucose. Our findings demonstrate that CD271 and pTrkA affect DM wound closure by promoting the eSC migration and proliferation. This mechanism involving the pERK, pAkt, and pJNK pathways might be a new therapeutic target for the treatment of delayed wound re-epithelialization in DM.
KeywordsCD271 Diabetes mellitus Epidermal stem cells Skin wound healing pTrkA
Epidermal growth receptor
Epidermal stem cells
Yibing Wang designed the experiments; Xiaohong Li, Min Zhang, and Mengyao Liu performed the experiments; Rui Zhang, Zhang Feng, Jiaxu Ma, Huayu Zhang, Kaifeng Huang, and Mengyao Liu contributed reagents, materials, analysis tools, added, and repeated the animal experiments; Mengyao Liu also edited the manuscript. Yongqian Cao and Siyuan Yin analyzed the data; Jun Ding, Xiaohong Li, Mengyao Liu, and Min Zhang wrote and reviewed the paper.
Science and Technology Development Program of Shandong Province (No. 2016GSF201080), and National Natural Science Foundation of China (No. 81772092 and 81571911) supported this study.
Compliance with ethical standards
Conflict of interests
The authors declare that there are no conflicts of interests.
According to the National Institutes of Health (NIH) Guide, all surgeries and experiments were performed under the pentobarbital sodium anesthesia, and followed the rules of the Committee on the Ethics of Shandong University.
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