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

✍ Scribed by Nalini M. Rajamannan; Malayannan Subramaniam; Theodore P. Abraham; Vlad C. Vasile; Michael J. Ackerman; David G. Monroe; Teng-Leong Chew; Thomas C. Spelsberg

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 539 KB
• Volume: 100
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21049

✦ Synopsis

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. J. Cell. Biochem. 100: 315–325, 2007. © 2006 Wiley‐Liss, Inc.