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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Bibliographic Details
Published in:PloS one 2017-07, Vol.12 (7), p.e0181945-e0181945
Main Authors: 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
Format: Article
Language:English
Subjects:
Accumulation
Animal models
Animals
Aorta - pathology
Biology and Life Sciences
Cancer
Cardiovascular disease
Cell Adhesion Molecules - metabolism
Chronic illnesses
Collagen
Constriction, Pathologic
Coronary artery disease
Disease Progression
Extracellular matrix
Extracellular Matrix Proteins - metabolism
Fibrosis
Genetic aspects
Growth factors
Heart
Heart attack
Heart attacks
Heart diseases
Heart failure
Heart Injuries - metabolism
Hospitals
Humans
Injuries
Laboratory animals
Medicine and Health Sciences
Mice
Mice, Transgenic
Myocardial infarction
Myocardial Infarction - metabolism
Organ Specificity
Overexpression
Pediatrics
Phenotype
Phenotypes
Proteins
Research and Analysis Methods
Rodents
Surgery
Transforming Growth Factor beta - metabolism
Transforming growth factor-b
Transforming growth factors
Transgenic animals
Transgenic mice
Ventricle
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0181945