| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Research Abstract |
Basic fibroblast growth factor (bFGF) is a mitogen that to playa important role in myocyte growth. In the first study, we found the increase of immunoreactivity of bFGF in cardiac myocyte of young SHR and pressure over-loaded rat heart, and it suggested that endogenous bFGF which contained high molecular form of bFGF contributes to myocardial hypertrophy. In the second study, rabdomyosarcoma (A204 cells) derived bFGF was used as wild type bFGF.A204 cells included high molecular form (22,24kD), as well as low molecular (18kD) bFGF by western blotting, and showed hypertrophied effect in cultured myocyte. The hypertrophic effects were indicated in remarkable enlargement of cell size and significant increase in accumulation of phenylalanin incorporation. The maximum expression of c-myc mRNA by A204 cell conditioned medium was observed 30 min after stimulation, and it was also accompanied by an increase of accumulation of alpha skeletal actin mRNA by primer extension. After absorption of he
… More
parin binding growth factor from A204 cnditioned medium, it indicated no hypertrophic effects. These finding suggests that endogenous high molecular form of bFGF produced by cardiomyocytes contributes to myocardial hypertrophy. In the third study, we investigated the expression and function of transforming beta1 (TGF-beta1) during evolving myocardial hypertrophy in cultured myocytes treated with norepinephrine (NE), angiotensin -II (A-II), Phorbor ester (PMA) and endogenous bFGF.NE,A-II,PMA and endogenous bFGF produced hypertrophy of cultured myocytes and induced expression of TGF-beta1 in the mRNA and protein level, determined by northern and western blotting analysis as well as immunohistorical staining. These agents also increased vascular extracellular components of fibronectin and laminin and the receptor, beta1-integrin. Recombinant TGF-beta1 had no effects of cardiac hypertrophy, whereas TGF-beta1 increased production of fibronectin, laminin and beta1-integrin in cultured cardiomyocytes. These observation indicates that endogenous TGF-beta1 is induced in cultured cardiomyocytes during the development of hypertrophy. TGF-beta1 acts on myocytes in autocrine manner and lead to production of extrcellular matrix and adhesion molecule. These findings suggest that TGF-beta1 produced by cardiomyocytes could contribute to the development of fibrosis and remodeling associated with cardiac hypertrophy. Less
|
