Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts

• Published in: Regulatory peptides 2005-01, Vol.124 (1), p.65-72
• Main Authors: Horio, Takeshi, Maki, Toshiyuki, Kishimoto, Ichiro, Tokudome, Takeshi, Okumura, Hiroyuki, Yoshihara, Fumiki, Suga, Shin-ichi, Takeo, Satoshi, Kawano, Yuhei, Kangawa, Kenji
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Antibodies - immunology; Autocrine Communication; Cell Size; Cells, Cultured; Dose-Response Relationship, Drug; Fibroblast; Fibroblasts - cytology; Fibroblasts - metabolism; Fibroblasts - secretion; Gene Expression Regulation; Growth factor; Hypertrophy; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - secretion; Muscle Cells - metabolism; Muscle Cells - secretion; Myocardium - cytology; Myocardium - metabolism; Myocardium - secretion; Myocyte; Paracrine; Paracrine Communication; Rats; Rats, Wistar
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2004.06.029

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.