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TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury

Extracellular matrix production and accumulation stabilize the heart under normal conditions as well as form a protective scar after myocardial infarction injury, although excessive extracellular matrix accumulation with long-standing heart disease is pathological. In the current study we investigat...

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Autores principales: Schwanekamp, Jennifer A., Lorts, Angela, Sargent, Michelle A., York, Allen J., Grimes, Kelly M., Fischesser, Demetria M., Gokey, Jason J., Whitsett, Jeffrey A., Conway, Simon J., Molkentin, Jeffery D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531541/
https://www.ncbi.nlm.nih.gov/pubmed/28750100
http://dx.doi.org/10.1371/journal.pone.0181945
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author Schwanekamp, Jennifer A.
Lorts, Angela
Sargent, Michelle A.
York, Allen J.
Grimes, Kelly M.
Fischesser, Demetria M.
Gokey, Jason J.
Whitsett, Jeffrey A.
Conway, Simon J.
Molkentin, Jeffery D.
author_facet Schwanekamp, Jennifer A.
Lorts, Angela
Sargent, Michelle A.
York, Allen J.
Grimes, Kelly M.
Fischesser, Demetria M.
Gokey, Jason J.
Whitsett, Jeffrey A.
Conway, Simon J.
Molkentin, Jeffery D.
author_sort Schwanekamp, Jennifer A.
collection PubMed
description Extracellular matrix production and accumulation stabilize the heart under normal conditions as well as form a protective scar after myocardial infarction injury, although excessive extracellular matrix accumulation with long-standing heart disease is pathological. In the current study we investigate the role of the matricellular protein, transforming growth factor beta-induced (TGFBI), which is induced in various forms of heart disease. Additionally, we sought to understand whether TGFBI is functionally redundant to its closely related family member periostin, which is also induced in the diseased heart. Surgical models of myocardial infarction and cardiac pressure overload were used in mice with genetic loss of Postn and/or Tgfbi to examine the roles of these genes during the fibrotic response. Additionally, cardiac-specific TGFBI transgenic mice were generated and analyzed. We observed that deletion of Tgfbi did not alter cardiac disease after myocardial infarction in contrast to greater ventricular wall rupture in Postn gene-deleted mice. Moreover, Tgfbi and Postn double gene-deleted mice showed a similar post-myocardial infarction disease phenotype as Postn-deleted mice. Over-expression of TGFBI in the hearts of mice had a similar effect as previously shown in mice with periostin over-expression. Thus, TGFBI and periostin act similarly in the heart in affecting fibrosis and disease responsiveness, although TGFBI is not seemingly necessary in the heart after myocardial infarction injury and is fully compensated by the more prominently expressed effector periostin.
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spelling pubmed-55315412017-08-07 TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury Schwanekamp, Jennifer A. Lorts, Angela Sargent, Michelle A. York, Allen J. Grimes, Kelly M. Fischesser, Demetria M. Gokey, Jason J. Whitsett, Jeffrey A. Conway, Simon J. Molkentin, Jeffery D. PLoS One Research Article Extracellular matrix production and accumulation stabilize the heart under normal conditions as well as form a protective scar after myocardial infarction injury, although excessive extracellular matrix accumulation with long-standing heart disease is pathological. In the current study we investigate the role of the matricellular protein, transforming growth factor beta-induced (TGFBI), which is induced in various forms of heart disease. Additionally, we sought to understand whether TGFBI is functionally redundant to its closely related family member periostin, which is also induced in the diseased heart. Surgical models of myocardial infarction and cardiac pressure overload were used in mice with genetic loss of Postn and/or Tgfbi to examine the roles of these genes during the fibrotic response. Additionally, cardiac-specific TGFBI transgenic mice were generated and analyzed. We observed that deletion of Tgfbi did not alter cardiac disease after myocardial infarction in contrast to greater ventricular wall rupture in Postn gene-deleted mice. Moreover, Tgfbi and Postn double gene-deleted mice showed a similar post-myocardial infarction disease phenotype as Postn-deleted mice. Over-expression of TGFBI in the hearts of mice had a similar effect as previously shown in mice with periostin over-expression. Thus, TGFBI and periostin act similarly in the heart in affecting fibrosis and disease responsiveness, although TGFBI is not seemingly necessary in the heart after myocardial infarction injury and is fully compensated by the more prominently expressed effector periostin. Public Library of Science 2017-07-27 /pmc/articles/PMC5531541/ /pubmed/28750100 http://dx.doi.org/10.1371/journal.pone.0181945 Text en © 2017 Schwanekamp et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schwanekamp, Jennifer A.
Lorts, Angela
Sargent, Michelle A.
York, Allen J.
Grimes, Kelly M.
Fischesser, Demetria M.
Gokey, Jason J.
Whitsett, Jeffrey A.
Conway, Simon J.
Molkentin, Jeffery D.
TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title_full TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title_fullStr TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title_full_unstemmed TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title_short TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury
title_sort tgfbi functions similar to periostin but is uniquely dispensable during cardiac injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531541/
https://www.ncbi.nlm.nih.gov/pubmed/28750100
http://dx.doi.org/10.1371/journal.pone.0181945
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