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The Heparanase Regulatory Network in Health and Disease

The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of vario...

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Autores principales: Mayfosh, Alyce J., Nguyen, Tien K., Hulett, Mark D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541136/
https://www.ncbi.nlm.nih.gov/pubmed/34681753
http://dx.doi.org/10.3390/ijms222011096
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author Mayfosh, Alyce J.
Nguyen, Tien K.
Hulett, Mark D.
author_facet Mayfosh, Alyce J.
Nguyen, Tien K.
Hulett, Mark D.
author_sort Mayfosh, Alyce J.
collection PubMed
description The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of various types of macromolecules including heparan sulfate proteoglycans (HSPGs). HSPGs comprise a protein core linked to the complex glycosaminoglycan heparan sulfate (HS), the remodeling of which is important for many physiological processes such as wound healing as well as pathological processes including cancer metastasis. Turnover of HS is tightly regulated by a single enzyme capable of cleaving HS side chains: heparanase. Heparanase upregulation has been identified in many inflammatory diseases including atherosclerosis, fibrosis, and cancer, where it has been shown to play multiple roles in processes such as epithelial-mesenchymal transition, angiogenesis, and cancer metastasis. Heparanase expression and activity are tightly regulated. Understanding the regulation of heparanase and its downstream targets is attractive for the development of treatments for these diseases. This review provides a comprehensive overview of the regulators of heparanase as well as the enzyme’s downstream gene and protein targets, and implications for the development of new therapeutic strategies.
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spelling pubmed-85411362021-10-24 The Heparanase Regulatory Network in Health and Disease Mayfosh, Alyce J. Nguyen, Tien K. Hulett, Mark D. Int J Mol Sci Review The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of various types of macromolecules including heparan sulfate proteoglycans (HSPGs). HSPGs comprise a protein core linked to the complex glycosaminoglycan heparan sulfate (HS), the remodeling of which is important for many physiological processes such as wound healing as well as pathological processes including cancer metastasis. Turnover of HS is tightly regulated by a single enzyme capable of cleaving HS side chains: heparanase. Heparanase upregulation has been identified in many inflammatory diseases including atherosclerosis, fibrosis, and cancer, where it has been shown to play multiple roles in processes such as epithelial-mesenchymal transition, angiogenesis, and cancer metastasis. Heparanase expression and activity are tightly regulated. Understanding the regulation of heparanase and its downstream targets is attractive for the development of treatments for these diseases. This review provides a comprehensive overview of the regulators of heparanase as well as the enzyme’s downstream gene and protein targets, and implications for the development of new therapeutic strategies. MDPI 2021-10-14 /pmc/articles/PMC8541136/ /pubmed/34681753 http://dx.doi.org/10.3390/ijms222011096 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mayfosh, Alyce J.
Nguyen, Tien K.
Hulett, Mark D.
The Heparanase Regulatory Network in Health and Disease
title The Heparanase Regulatory Network in Health and Disease
title_full The Heparanase Regulatory Network in Health and Disease
title_fullStr The Heparanase Regulatory Network in Health and Disease
title_full_unstemmed The Heparanase Regulatory Network in Health and Disease
title_short The Heparanase Regulatory Network in Health and Disease
title_sort heparanase regulatory network in health and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541136/
https://www.ncbi.nlm.nih.gov/pubmed/34681753
http://dx.doi.org/10.3390/ijms222011096
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