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Vitamin C-induced gene expression profiling in GM5659 human skin fibroblasts

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE11919 | GEO | 2009/02/10

SECONDARY ACCESSION(S): PRJNA105761

REPOSITORIES: GEO

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Project description:This a model from the article: Modeling the effects of treating diabetic wounds with engineered skin substitutes. Waugh HV, Sherratt JA. Wound Repair Regen 2007 Jul-Aug;15(4):556-65 17650100 , Abstract: In this paper, a novel mathematical model of wound healing in both normal and diabetic cases is presented, focusing upon the effects of adding two currently available commercial engineered skin substitute therapies to the wound (Apligraf) and Dermagraft). Our work extends a previously developed model, which considers inflammatory and repair macrophage dynamics in normal and diabetic wound healing. Here, we extend the model to include equations for platelet-derived growth factor concentration, fibroblast density, collagen density, and hyaluronan concentration. This enables us to examine the variation of these components in both normal and diabetic wound healing cases, and to model the treatment protocols of these therapies. Within the context of our model, we find that the key component to successful healing in diabetic wounds is hyaluronan and that the therapies work by increasing the amount of hyaluronan available in the wound environment. The time-to-healing results correlate with those observed in clinical trials and the model goes some way to establishing an understanding of why diabetic wounds do not heal, and how these treatments affect the diabetic wound environment to promote wound closure. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Waugh HV, Sherratt JA. (2007) - version=1.0 The original CellML model was created by: Catherine Lloyd c.lloyd@auckland.ac.nz The University of Auckland This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Vitamin C-induced gene expression profiling in GM5659 human skin fibroblasts

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