ILB® resolves inflammatory scarring and promotes functional tissue repair

Abstract Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular dis...

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Autores principales:	Lisa J. Hill, Hannah F. Botfield, Ghazala Begum, Omar Qureshi, Vasanthy Vigneswara, Imran Masood, Nicholas M. Barnes, Lars Bruce, Ann Logan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/2442875be5214f76ad6435f0b821009d
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spelling	oai:doaj.org-article:2442875be5214f76ad6435f0b821009d2021-12-02T13:49:54ZILB® resolves inflammatory scarring and promotes functional tissue repair10.1038/s41536-020-00110-22057-3995https://doaj.org/article/2442875be5214f76ad6435f0b821009d2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41536-020-00110-2https://doaj.org/toc/2057-3995Abstract Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB®, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo. Of particular relevance, we demonstrated that ILB® acts, in part, by downregulating transforming growth factor (TGF)β signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis and functional tissue regeneration. These observations indicate the potential of ILB® to alleviate fibrotic diseases.Lisa J. HillHannah F. BotfieldGhazala BegumOmar QureshiVasanthy VigneswaraImran MasoodNicholas M. BarnesLars BruceAnn LoganNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Lisa J. Hill Hannah F. Botfield Ghazala Begum Omar Qureshi Vasanthy Vigneswara Imran Masood Nicholas M. Barnes Lars Bruce Ann Logan ILB® resolves inflammatory scarring and promotes functional tissue repair
description	Abstract Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB®, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo. Of particular relevance, we demonstrated that ILB® acts, in part, by downregulating transforming growth factor (TGF)β signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis and functional tissue regeneration. These observations indicate the potential of ILB® to alleviate fibrotic diseases.
format	article
author	Lisa J. Hill Hannah F. Botfield Ghazala Begum Omar Qureshi Vasanthy Vigneswara Imran Masood Nicholas M. Barnes Lars Bruce Ann Logan
author_facet	Lisa J. Hill Hannah F. Botfield Ghazala Begum Omar Qureshi Vasanthy Vigneswara Imran Masood Nicholas M. Barnes Lars Bruce Ann Logan
author_sort	Lisa J. Hill
title	ILB® resolves inflammatory scarring and promotes functional tissue repair
title_short	ILB® resolves inflammatory scarring and promotes functional tissue repair
title_full	ILB® resolves inflammatory scarring and promotes functional tissue repair
title_fullStr	ILB® resolves inflammatory scarring and promotes functional tissue repair
title_full_unstemmed	ILB® resolves inflammatory scarring and promotes functional tissue repair
title_sort	ilb® resolves inflammatory scarring and promotes functional tissue repair
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2442875be5214f76ad6435f0b821009d
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ILB® resolves inflammatory scarring and promotes functional tissue repair

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