Substance P accelerates wound healing in type 2 diabetic mice through endothelial progenitor cell mobilization and Yes-associated protein activation

Um,Jihyun; Yu,Jinyeong; Park,Ki‑Sook

doi:10.3892/mmr.2017.6344

Substance P accelerates wound healing in type 2 diabetic mice through endothelial progenitor cell mobilization and Yes-associated protein activation

Authors:
- Jihyun Um
- Jinyeong Yu
- Ki‑Sook Park
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Affiliations: Graduate School of Biotechnology, Kyung Hee University, Yongin, Gyeonggi 17104, Republic of Korea, East‑West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea
Published online on: March 21, 2017 https://doi.org/10.3892/mmr.2017.6344
Pages: 3035-3040
Copyright: © Um et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Wound healing is delayed in diabetes due to a number of factors, including impaired angiogenesis and poor dermal healing. The present study demonstrated that subcutaneous administration of substance P (SP) accelerates wound healing in db/db type 2 diabetic mice (db/db mice). SP injection (10 nM/kg, subcutaneously) enhanced angiogenesis, induced the mobilization of endothelial progenitor cells (EPCs) and increased the number of EPC‑colony forming units (EPC‑CFUs) in the bone marrow of db/db mice. Immunohistochemistry was performed to check the effects of SP on the cellular proliferation and the subcellular localization of Yes-associated protein (YAP) in the wound dermis. SP also upregulated cellular proliferation in the injured dermis of db/db mice. Compared with the control group, an increased number of cells in the wound dermis of SP-treated mice exhibited nuclear localization of YAP, which induces cellular proliferation. The results of the current study indicate that subcutaneous administration of SP may be a promising therapeutic strategy to treat diabetic wounds exhibiting impaired angiogenesis and dysfunctional dermal wound healing.

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