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

Jennifer A. Schwanekamp, Angela Lorts, Michelle A. Sargent, Allen J. York, Kelly M. Grimes, Demetria M. Fischesser, Jason J. Gokey, Jeffrey A. Whitsett, Simon J. Conway, Jeffery D. Molkentin

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere0181945
JournalPLoS ONE
Volume12
Issue number7
DOIs
StatePublished - Jul 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Schwanekamp, J. A., Lorts, A., Sargent, M. A., York, A. J., Grimes, K. M., Fischesser, D. M., Gokey, J. J., Whitsett, J. A., Conway, S. J., & Molkentin, J. D. (2017). TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury. PLoS ONE, 12(7), [e0181945]. https://doi.org/10.1371/journal.pone.0181945