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Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors

Rolfe, KJ; Cambrey, AD; Richardson, J; Irvine, LM; Grobbelaar, AO; Linge, C; (2007) Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors. BMC DEV BIOL , 7 , Article 124. 10.1186/1471-213X-7-124. Green open access

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Abstract

Background: It has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal (< 14 weeks) and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis.Results: We have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 ( p44) in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II.Conclusion: Dermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.

Type: Article
Title: Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-213X-7-124
Publisher version: http://dx.doi.org/10.1186/1471-213X-7-124
Language: English
Additional information: © 2007 Rolfe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HYPERTROPHIC SCAR TISSUE, FACTOR-I RECEPTOR, IGF-I, MESSENGER-RNA, SIGNAL-TRANSDUCTION, MYOFIBROBLAST DIFFERENTIATION, INTESTINAL FIBROBLASTS, BINDING-PROTEINS, HUMAN-FETUS, MAP KINASE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/119814
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