title: Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro.
abstract: Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin-eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Tonglie
authors.initials: T
authors.lastname: Huang
authors.affiliation: National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, People's Republic of China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Wangqian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D000468:Alkalies; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000468:Alkalies; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157
keywords: ERK1/2 signaling pathway; human umbilical vein endothelial cells; pentadecapeptide BPC-157; wound healing