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Investigation of keratinocyte regulation of collagen I synthesis by dermal fibroblasts in a simple in vitro model
journal contribution
posted on 2017-05-12, 13:24 authored by C.A. Harrison, F. Gossiel, A.J. Bullock, Tao SunTao Sun, A. Blumsohn, Sheila MacNeilBackground Hypertrophic scarring and skin graft contracture are major causes of morbidity after burn injuries. A prominent feature is excessive fibroplasia with accumulation of increased fibrillar collagen relative to normal scar tissue. The application of split-thickness skin grafts or cultured epithelial autografts to burn wounds is known to reduce scarring and contraction.
Objectives To investigate further how the keratinocyte influences underlying fibroblast behaviour by examining the influence of keratinocytes on fibroblast collagen synthesis, using a new assay for collagen synthesis never previously applied to skin cell biology.
Methods We investigated the influence of the keratinocyte on fibroblast synthesis of type I collagen using an immunoassay for the aminoterminal propeptide of type I collagen (P1NP) in conditioned medium from monocultures and cocultures of keratinocytes and fibroblasts over 14 days. The importance of the physical presence of the keratinocyte was investigated by comparing cocultures of keratinocytes and fibroblasts against fibroblast monocultures with keratinocyte-conditioned medium. Pharmacological agents known to promote fibroblast proliferation [basic fibroblast growth factor (bFGF)], keratinocyte proliferation [insulin-like growth factor (IGF)-1], modify scarring in vivo[tumour necrosis factor (TNF)-α] or modify collagen biochemistry [putrescine, estrone, estradiol and β-aminopropionitrile (β-APN)] were then investigated for their effect on collagen synthesis in fibroblasts and in keratinocyte/fibroblast cocultures.
Results Keratinocytes in coculture with fibroblasts, and keratinocyte-conditioned medium, both reduced fibroblast P1NP synthesis. Of the pharmacological agents investigated, bFGF, IGF-1, TNF-α and β-APN all increased collagen synthesis both in monocultures of fibroblasts and in cocultures of keratinocytes and fibroblasts.
Conclusions Fibroblast collagen synthesis appears to be downregulated by keratinocyte-derived cytokines. Fibroblast growth factors and proinflammatory cytokines appear to be able partially to overcome this downregulation and to increase collagen synthesis.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
British Journal of DermatologyVolume
154Issue
3Pages
401 - 410Citation
HARRISON, C.A, 2006. Investigation of keratinocyte regulation of collagen I synthesis by dermal fibroblasts in a simple in vitro model. British Journal of Dermatology, 154 (3), pp.401-410Publisher
© WileyVersion
- NA (Not Applicable or Unknown)
Publisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2006Notes
This paper is closed access.ISSN
0007-0963eISSN
1365-2133Publisher version
Language
- en