title: N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells.
abstract: Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro. Knockdown of CXCR2 expression in hEPCs abrogated the stimulatory effects of Ac-PGP on migration and tube formation. In a cutaneous wound healing model of rats and mice, topical application of Ac-PGP accelerated cutaneous wound healing with promotion of neovascularization. The positive effects of Ac-PGP on wound healing and neovascularization were blocked in CXCR2 knockout mice. In nude mice, the individual application of Ac-PGP treatment or hEPC injection accelerated wound healing by increasing neovascularization. Moreover, the combination of Ac-PGP treatment and hEPC injection further stimulated wound healing and neovascularization. Topical administration of Ac-PGP onto wound bed stimulated migration and engraftment of transplanted hEPCs into cutaneous dermal wounds. Therefore, these results suggest novel applications of Ac-PGP in promoting wound healing and augmenting the therapeutic efficacy of hEPCs.
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Yang Woo
authors.initials: YW
authors.lastname: Kwon
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Tae Wook
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Gyu Tae
authors.initials: GT
authors.lastname: Park
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Yoon
authors.affiliation: Department of Oral Biochemistry and Molecular Biology, Pusan National University School of Dentistry, Yangsan 50612, Republic of Korea.
authors.forename: Il Ho
authors.initials: IH
authors.lastname: Jang
authors.affiliation: Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Hyun-Chang
authors.initials: HC
authors.lastname: Ko
authors.affiliation: Korea Brain Research Institute, Daegu 41068, Republic of Korea.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Korea Brain Research Institute, Daegu 41068, Republic of Korea.
authors.forename: Hyeona
authors.initials: H
authors.lastname: Kang
authors.affiliation: Korea Brain Research Institute, Daegu 41068, Republic of Korea.
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.affiliation: Functional Genomics Research Center, KRIBB, Daejeon 34141, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.|Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000502:physiology*; D018345:Mice, Knockout; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D009842:Oligopeptides; D023063:Receptors, Interleukin-8B; C113164:prolyl-glycyl-proline; D011392:Proline