TY - JOUR
T1 - TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy
T2 - Discovery and characterization of a novel signaling pathway
AU - Rajamannan, Nalini M.
AU - Subramaniam, Malayannan
AU - Abraham, Theodore P.
AU - Vasile, Vlad C.
AU - Ackerman, Michael J.
AU - Monroe, David G.
AU - Chew, Teng Leong
AU - Spelsberg, Thomas C.
PY - 2007/2/1
Y1 - 2007/2/1
N2 - 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.
AB - 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.
KW - Cardial hypertrophy
KW - PTTG-1
KW - TIEG
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U2 - 10.1002/jcb.21049
DO - 10.1002/jcb.21049
M3 - Article
C2 - 16888812
AN - SCOPUS:33846463777
SN - 0730-2312
VL - 100
SP - 315
EP - 325
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - 2
ER -