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 John Ackerman, David G Monroe, Teng Leong Chew, Thomas C. Spelsberg

Research output: Contribution to journalArticle

39 Citations (Scopus)

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

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Cardiomegaly
Genes
Pituitary Neoplasms
Oncogenes
Gene Knockout Techniques
Knockout Mice
Hypertrophy
Tumors
Fibrosis
Microarrays
Myofibroblasts
Microarray Analysis
Tissue
Histones
Muscle Cells
Heart Ventricles
Echocardiography
Immunohistochemistry
Body Weight
Staining and Labeling

Keywords

  • Cardial hypertrophy
  • PTTG-1
  • TIEG

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy : Discovery and characterization of a novel signaling pathway. / Rajamannan, Nalini M.; Subramaniam, Malayannan; Abraham, Theodore P.; Vasile, Vlad C.; Ackerman, Michael John; Monroe, David G; Chew, Teng Leong; Spelsberg, Thomas C.

In: Journal of Cellular Biochemistry, Vol. 100, No. 2, 01.02.2007, p. 315-325.

Research output: Contribution to journalArticle

Rajamannan, Nalini M. ; Subramaniam, Malayannan ; Abraham, Theodore P. ; Vasile, Vlad C. ; Ackerman, Michael John ; Monroe, David G ; Chew, Teng Leong ; Spelsberg, Thomas C. / TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy : Discovery and characterization of a novel signaling pathway. In: Journal of Cellular Biochemistry. 2007 ; Vol. 100, No. 2. pp. 315-325.
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