Substance P accelerates wound healing in type 2 diabetic mice through endothelial progenitor cell mobilization and Yes-associated protein activation.
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.
Graduate School of Biotechnology, Kyung Hee University, Yongin, Gyeonggi 17104, Republic of Korea.
Jihyun
J
Um
Graduate School of Biotechnology, Kyung Hee University, Yongin, Gyeonggi 17104, Republic of Korea.
Jinyeong
J
Yu
East‑West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea.
Ki-Sook
KS
Park
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011897:Random Allocation; D013373:Substance P / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D013373:Substance P