Insulin-like growth factor-binding protein-3 induces fetalization in neonatal rat cardiomyocytes.
We employed cDNA microarrays representing 4000 distinct sequences to profile changes in gene expression in a rodent model of heart disease, namely, progression to heart failure after myocardial infarction. Differential gene expression in the left ventricle was examined at 4-week intervals over a 12-week period after coronary artery ligation in rats. Over this time course, insulin-like growth factor-binding protein-3 (IGFBP-3) was found to have a greater expression than in nondiseased tissues. We then employed quantitative real-time PCR to analyze gene expression in neonatal rat cardiac myocytes that had been treated with recombinantly expressed IGFBP-3 to examine a number of transcriptional responses designed to reflect the heart failure phenotype. The IGFBP-3 protein was shown to induce transcription of atrial natriuretic factor (ANF) and beta-myosin heavy chain (B-MHC). Analysis of conditioned media taken from IGFBP-3-treated cardiac myocyte cultures demonstrated an increase in ANF protein as well as in protein synthesis, as determined by metabolic incorporation of a radiolabeled amino acid. However, transcriptional changes of troponin-1, endothelin-1, or angiotensin-II by IGFBP-3 were not observed.
Henson
M
M
Scios Inc., 820 W. Maude Ave., Sunnyvale, CA 94086, USA.
Damm
D
D
Lam
A
A
Garrard
L J
LJ
White
T
T
Abraham
J A
JA
Schreiner
G F
GF
Stanton
L W
LW
Joly
A H
AH
D000804:Angiotensin II / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D019332:Endothelin-1 / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000196:embryology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009203:Myocardial Infarction / Q000235:genetics*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D019210:Troponin I / Q000235:genetics
D019332:Endothelin-1; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019210:Troponin I; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains