title: Recombinant growth factor mixtures induce cell cycle progression and the upregulation of type I collagen in human skin fibroblasts, resulting in the acceleration of wound healing processes.
abstract: Application of growth factor mixtures has been used for wound healing and anti-wrinkles agents. The aim of this study was to evaluate the effect of recombinant growth factor mixtures (RGFM) on the expression of cell cycle regulatory proteins, type I collagen, and wound healing processes of acute animal wound models. The results showed that RGFM induced increased rates of cell proliferation and cell migration of human skin fibroblasts (HSF). In addition, expression of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)4, and Cdk2 proteins was markedly increased with a growth factor mixtures treatment in fibroblasts. Expression of type I collagen was also increased in growth factor mixtures-treated HSF. Moreover, growth factor mixtures-induced the upregulation of type I collagen was associated with the activation of Smad2/3. In the animal model, RGFM-treated mice showed accelerated wound closure, with the closure rate increasing as early as on day 7, as well as re-epithelization and reduced inflammatory cell infiltration than phosphate-buffered saline (PBS)-treated mice. In conclusion, the results indicated that RGFM has the potential to accelerate wound healing through the upregulation of type I collagen, which is partly mediated by activation of Smad2/3-dependent signaling pathway as well as cell cycle progression in HSF. The topical application of growth factor mixtures to acute and chronic skin wound may accelerate the epithelization process through these molecular mechanisms.
authors.affiliation: Nutrex Technology R&D Center, Seoul, Republic of Korea.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jae-We
authors.initials: JW
authors.lastname: Cho
authors.affiliation: Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Convergence Medicine and Pharmaceutical Biosciences, Graduate School, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Tae Rin
authors.initials: TR
authors.lastname: Kwon
authors.affiliation: Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Cosmeceutical Team, Pacific Pharmaceuticals, Seoul, Republic of Korea.
authors.forename: Yoo Mi
authors.initials: YM
authors.lastname: Choi
authors.affiliation: Marketing and Business Division, Pacific Pharmaceuticals, Seoul, Republic of Korea.
authors.forename: Jay
authors.initials: J
authors.lastname: Lee
authors.affiliation: MB Business Development Team, Pacific Pharmaceuticals, Seoul, Republic of Korea.
authors.forename: Ho Sang
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Beom Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000494:pharmacology; D051379:Mice; D012867:Skin / Q000166:cytology*; D013002:Somatomedins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D024042:Collagen Type I; D013002:Somatomedins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D013482:Superoxide Dismutase; D020781:Matrix Metalloproteinase 1