title: The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells.
abstract: Although adipose-derived stem cells (ASCs) show promise for cell therapy, there is a tremendous need for developing ASC activators. In the present study, we investigated whether or not vitamin C increases the survival, proliferation, and hair-regenerative potential of ASCs. In addition, we tried to find the molecular mechanisms underlying the vitamin C-mediated stimulation of ASCs. Sodium-dependent vitamin C transporter 2 (SVCT2) is expressed in ASCs, and mediates uptake of vitamin C into ASCs. Vitamin C increased the survival and proliferation of ASCs in a dose-dependent manner. Vitamin C increased ERK1/2 phosphorylation, and inhibition of the mitogen-activated protein kinase (MAPK) pathway attenuated the proliferation of ASCs. Microarray and quantitative polymerase chain reaction showed that vitamin C primarily upregulated expression of proliferation-related genes, including Fos, E2F2, Ier2, Mybl1, Cdc45, JunB, FosB, and Cdca5, whereas Fos knock-down using siRNA significantly decreased vitamin C-mediated ASC proliferation. In addition, vitamin C-treated ASCs accelerated the telogen-to-anagen transition in C3H/HeN mice, and conditioned medium from vitamin C-treated ASCs increased the hair length and the Ki67-positive matrix keratinocytes in hair organ culture. Vitamin C increased the mRNA expression of HGF, IGFBP6, VEGF, bFGF, and KGF, which may mediate hair growth promotion. In summary, vitamin C is transported via SVCT2, and increased ASC proliferation is mediated by the MAPK pathway. In addition, vitamin C preconditioning enhanced the hair growth promoting effect of ASCs. Because vitamin C is safe and effective, it could be used to increase the yield and regenerative potential of ASCs.
authors: 1 Department of Applied Bioscience, CHA University , Seoul, Korea.
authors: Ji Hye
authors: JH
authors: Kim
authors: Wang-Kyun
authors: WK
authors: Kim
authors: Young Kwan
authors: YK
authors: Sung
authors: Mi Hee
authors: MH
authors: Kwack
authors: Seung Yong
authors: SY
authors: Song
authors: Joon-Seok
authors: JS
authors: Choi
authors: Sang Gyu
authors: SG
authors: Park
authors: TacGhee
authors: T
authors: Yi
authors: Hyun-Joo
authors: HJ
authors: Lee
authors: Dae-Duk
authors: DD
authors: Kim
authors: Hyun Min
authors: HM
authors: Seo
authors: Sun U
authors: SU
authors: Song
authors: Jong-Hyuk
authors: JH
authors: Sung
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D006197:Hair / Q000187:drug effects / Q000254:growth & development*; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D014176:Protein Biosynthesis; D060347:Sodium-Coupled Vitamin C Transporters / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid