Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.

We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracel...

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Main Authors: Dallon, J, Sherratt, J, Maini, P
Format: Journal article
Language:English
Published: 2001
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author Dallon, J
Sherratt, J
Maini, P
author_facet Dallon, J
Sherratt, J
Maini, P
author_sort Dallon, J
collection OXFORD
description We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed. Here we extend the model by allowing a time varying concentration of TGFbeta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFbeta profile. Within this model framework we find that most of the known effects of TGFbeta, i.e., changes in cell motility, cell proliferation and collagen production, are of minor importance to matrix alignment and cannot explain the anti-scarring properties of TGFbeta. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGFbeta on scarring.
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spelling oxford-uuid:baeedd0f-24c7-4f16-972d-d94c6f8f7fd32022-03-27T05:13:13ZModeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:baeedd0f-24c7-4f16-972d-d94c6f8f7fd3EnglishSymplectic Elements at Oxford2001Dallon, JSherratt, JMaini, PWe present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed. Here we extend the model by allowing a time varying concentration of TGFbeta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFbeta profile. Within this model framework we find that most of the known effects of TGFbeta, i.e., changes in cell motility, cell proliferation and collagen production, are of minor importance to matrix alignment and cannot explain the anti-scarring properties of TGFbeta. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGFbeta on scarring.
spellingShingle Dallon, J
Sherratt, J
Maini, P
Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title_full Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title_fullStr Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title_full_unstemmed Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title_short Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
title_sort modeling the effects of transforming growth factor beta on extracellular matrix alignment in dermal wound repair
work_keys_str_mv AT dallonj modelingtheeffectsoftransforminggrowthfactorbetaonextracellularmatrixalignmentindermalwoundrepair
AT sherrattj modelingtheeffectsoftransforminggrowthfactorbetaonextracellularmatrixalignmentindermalwoundrepair
AT mainip modelingtheeffectsoftransforminggrowthfactorbetaonextracellularmatrixalignmentindermalwoundrepair