Hypertrophy of cultured adult rat ventricular cardiomyocytes induced by antibodies against the insulin-like growth factor (IGF)-I or the IGF-I receptor is IGF-II-dependent.
Antibodies against the insulin-like growth factor-I (IGF-I) or the IGF-I receptor (IGF-IR) directly initiate a rapid (within 6 h) hypertrophy of isolated adult rat ventricular cardiomyocytes cultured in the absence of serum. Further, cardiomyocytes treated with either of these agonistic antibodies upregulate the expression of their genes for insulin-like growth factor-II (IGF-II) and the IGF-II receptor (IGF-IIR). Genistein, an inhibitor of the tyrosine kinase IGF-IR, also induces the cardiomyocytes to hypertrophy. Anti-IGF-II antibody inhibits the cardiomyocyte hypertrophy induced by anti-IGF-I and anti-IGF-IR antibodies or by genistein. Results are consistent with a model in which local production of IGF-II is upregulated when the IGF-IR signaling pathway is blocked and in which an IGF-II-mediated pathway, likely involving the IGF-IIR, then stimulates hypertrophy of the cardiomyocytes.
Huang
Chih-Yang
CY
Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA.
Hao
Ling-Yang
LY
Buetow
Dennis E
DE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D019833:Genistein / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D019833:Genistein; D017526:Receptor, IGF Type 1