| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Lens epithelial cells can survive for weeks in high density culture in the absence of exogenous signaling molecules. They don t, however, proliferate or differentiate into lens fibers, unless exogenous signaling molecules are added (Ishizaki et al.J.Cell Biol.121 : 899-908, 1993). In the presence of basic fibroblast growth factor (bFGF), they proliferate at first, but they eventually stop dividing, and begin to differentiate into lens fibers. It is not known how they stop dividing and begin to differentiate into lens fibers in the presence of mitogens. In this project I tried to test my hypotheses that lens epithelial cells can divide only for the limited number of times even in the presence of potent mitogens, that cyclin-dependent kinase inhibitors are involved in the stopping mechanism, and that lens epithelial cells begin to differentiate into lens fibers spontaneously when they stop dividing.
In the presence of higher concentrations of bFGF, differentiation as well as proliferation of lens epithelial cells was stimulated, and accumulation of p27/Kip1, a cyclin-dependent kinase inhibitor, in their nuclei was observed. In the presence of IGF-1 or lower concentrations of bFGF, by contrast, only proliferation of these cells was stimulated. The cells, however, eventually stopped dividing even in the presence of these mitogens, expressing p27/Kip1 in their nuclei. Taken together, these results suggest that lens epithelial cells can divide only for the limited number of times even in the presence of potent mitogens, and that p27Kip1 is involved in this restriction of lens epithelial cell proliferation. The results also suggest that lens epithelial cells don t differentiate into lens fibers spontaneously when they stop dividing. I will investigate the mechanism of p27/Kip1 accumulation in lens epithelial cells. I will also investigate the mechanism whereby lens epithelial cells begin to differentiate into lens fibers.
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