Gene expression profiling reveals new protective roles for vitamin C in human skin cells.
The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and, consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with "scorbutic" cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways.
Duarte
Tiago L
TL
Department of Cancer Studies and Molecular Medicine, University of Leicester, UK. tduarte@ibmc.up.pt
Cooke
Marcus S
MS
Jones
George D D
GD
D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003260:Contact Inhibition; D019610:Cytoprotection; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016195:G2 Phase; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
D018797:Cell Cycle Proteins; C011669:ascorbate-2-phosphate; D001205:Ascorbic Acid