title: Platelet-rich plasma stimulates human dermal fibroblast proliferation via a Ras-dependent extracellular signal-regulated kinase 1/2 pathway.
abstract: Platelet-rich plasma (PRP) contains a high concentration of several growth factors and contributes to soft-tissue engineering and wound healing. However, the effect of PRP on human dermal fibroblast proliferation and responses is unknown. This was investigated in the present study using PRP prepared from the whole human blood using the double-spin method. Human dermal fibroblast cultures were established from skin samples collected during plastic surgery. Platelet concentration and growth factor levels in PRP were estimated, and a cell proliferation assay was carried out after PRP treatment. The role of Ras-dependent extracellular signal-regulated kinase (ERK)1/2 in the effects of PRP was investigated in human dermal fibroblasts by suppressing ERK1/2 expression with an inhibitor or by short interfering (si)RNA-mediated knockdown, and assessing ERK1/2 phosphorylation by western blotting as well as proliferation in PRP-treated cells. We found that PRP stimulated human dermal fibroblast proliferation, which was suppressed by ERK1/2 inhibitor treatment (P < 0.01). ERK1/2 phosphorylation was increased in the presence of PRP, while siRNA-mediated knockdown of ERK1/2 blocked cell proliferation normally induced by PRP treatment (P < 0.01). These results demonstrate that PRP induces human dermal fibroblast proliferation via activation of ERK1/2 signaling. Our findings provide a basis for the development of agents that can promote wound healing and can be applied to soft-tissue engineering.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. hara-t@cc.osaka-dent.ac.jp.|Department of Oral Implantology, Osaka Dental University, 1-5-17 Otemae, Chuo-ku, Osaka, 540-0008, Japan. hara-t@cc.osaka-dent.ac.jp.
authors.forename: Tomoya
authors.identifier: http://orcid.org/0000-0003-0450-6829
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. kakudon@hirakata.kmu.ac.jp.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kakudo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Lai
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kusumoto
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3; D010766:Phosphorylation; D053657:Platelet-Rich Plasma / Q000502:physiology*; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK1/2; Fibroblasts; Platelet-rich plasma; Proliferation