TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway

Nalini M. Rajamannan, Malayannan Subramaniam, Theodore P. Abraham, Vlad C. Vasile, Michael J. Ackerman, David G. Monroe, Teng Leong Chew, Thomas C. Spelsberg

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFβ inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG -/- knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG-/- knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG-/-, and an increase in wall thickness in TIEG-/- mice of (1.85 ± 0.21 mm), compared to the control (1.13 ± 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG-/- heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG-/- mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse.

Original languageEnglish (US)
Pages (from-to)315-325
Number of pages11
JournalJournal of cellular biochemistry
Volume100
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Cardial hypertrophy
  • PTTG-1
  • TIEG

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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