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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 12.05.2017, 13:24 authored by C.A. Harrison, F. Gossiel, A.J. Bullock, Tao SunTao Sun, A. Blumsohn, Sheila MacNeil
Background  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.



  • Aeronautical, Automotive, Chemical and Materials Engineering


  • Chemical Engineering

Published in

British Journal of Dermatology






401 - 410


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.401-410


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