Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts.
Insulin-like growth factor (IGF)-1 appears to play an important role in cardiac hypertrophy or remodeling. However, the role of endogenous IGF-1 in the growth of cardiac myocytes and fibroblasts remains unclear. This study investigated the major site of the production of cardiac IGF-1 and the local effects of endogenous IGF-1 secreted from cardiac cells. A significant expression of IGF-1 mRNA was found in cultured neonatal and adult rat cardiac fibroblasts, but not in myocytes. In addition, an in vivo examination by in situ hybridization histochemical analyses demonstrated the IGF-1 transcripts in the interstitial fibrotic tissue of the ventricle. Time-dependent secretion of IGF-1 protein was also observed in cultured cardiac fibroblasts. An antibody against IGF-1 decreased collagen synthesis in cardiac fibroblasts under basal conditions. Fibroblast-conditioned medium, as well as exogenous IGF-1, increased protein synthesis in cardiac myocytes, and this increase was inhibited by antibodies against IGF-1 and IGF-1 receptor, IGF binding protein-3, and IGF-1 receptor antagonist. These observations suggest that IGF-1 is produced and released mainly from cardiac fibroblasts and that endogenous IGF-1 promotes collagen synthesis by cardiac fibroblasts and hypertrophy of myocytes as an autocrine and a paracrine factor. Cardiac IGF-1 may function as an endogenous modulator of cardiac hypertrophy or remodeling.
Horio
Takeshi
T
Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan. thorio@ri.ncvc.go.jp
Maki
Toshiyuki
T
Kishimoto
Ichiro
I
Tokudome
Takeshi
T
Okumura
Hiroyuki
H
Yoshihara
Fumiki
F
Suga
Shin-ichi
S
Takeo
Satoshi
S
Kawano
Yuhei
Y
Kangawa
Kenji
K
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology; D019898:Autocrine Communication; D048429:Cell Size; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D032342:Muscle Cells / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D019899:Paracrine Communication; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D007334:Insulin-Like Growth Factor I