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 processess

Abstract

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 mixturestreated 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 phosphatebuffered 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.

Modulation of adenine phosphoribosyltransferase‐mediated salvage pathway to accelerate diabetic wound healing

“…All mice were anaesthetized intraperitoneal injection of a combination of zolazepam and tiletamine as Zoletil 50 (30 mg/kg, Virbac, Carros, France) and xylazine as Rompun (10 mg/kg, Bayer, Leverkusen, Germany) 26 . Before surgery, the hair was shaved from the dorsal surface of mice.…”

Helium/Argon-Generated Cold Atmospheric Plasma Facilitates Cutaneous Wound Healing

“…Downregulation of E-cadherin enhances wound re-epithelialization (Terao et al, 2011), which is crucial for promoting epidermal cell migration and tissue repair (Haensel and Dai, 2018). The expression levels of cyclin D1 and Cdk2 are increased and drive the G1/S phase transition of the cell cycle, thereby enforcing cell proliferation (Lee et al, 2014). In addition, the activation of the ERK family, which is involved in the MAPK pathways, plays a pivotal role in the regulation of cell proliferation (Escuin-Ordinas et al, 2016).…”

Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration

“…Additionally, low-molecular-weight protamine can be conjugated to the N-terminal sequence of EGF to enhance EGF penetration without reducing its biological activity [ 116 , 117 ]. Besides single growth factor therapy, the effect of recombinant growth factor mixtures on the proliferation and migration of human skin fibroblasts, expression of cell cycle regulatory proteins or type I collagen, and acceleration of wound healing has been evaluated in animal models [ 142 ]. Combination therapy of deciduous teeth dental pulp cell transplantation and bFGF solution has also been examined for wound healing of skin defects in nude mice [ 143 ].…”