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Insulin-Like Growth Factor-I Stimulates Fibronectin Gene Expression in Rat Vascular Smooth Muscle Cells and Glomerular Mesangial Cells

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Uniformed Services University Of The Health Sciences Bethesda United States

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Elevated fibronectin levels have been observed in the matrix of diabetic blood vessels and renal glomeruli. Growth factors have been implicated as possible regulators of matrix production. Therefore, the role of Insulin-Like Growth Factor-I IGF-I on fibronectin gene expression and synthesis in rat thoracic aortic vascular smooth muscle cells SMC and glomerular mesangial cells Me was investigated . Northern blot analysis demonstrated a time and dose-dependent increase of fibronectin mRNA levels. Significant levels P0.05 were observed 4 hours SMC and 8 hours MC after the addition of an optimum dose of 10 ngml IGF-I. When incubated in the presence of actinomycin D and IGF-I, the fibronectin response was blocked. However, cycloheximide and IGF-I increased fibronectin mRNA levels even more than the response induced by the growth factor alone. These results suggest transcriptional and translational control by I GF-I. Westernand slot blot analysis demonstrated a 25 P 0 . 05 and 29 P0.01 increase in fibronectin secreted into the SMC culture media 4 and 8 hours after IGF-I addition, respectively. IGF-I had no effect on cellular SMC fibronectin levels. However, a 22 P0.01 , 32 P0.01, and 19 P0.01 increase in cellular MC fibronectin levels were observed after 4, 8, and 12 hours of IGF-I treatment, respectively. A 46 increase P0.01 of fibronectin secreted into the culture media 8hours after IGF-I addition was also observed. The fibronectin mRNA and protein synthesis by both cell types were specific for IGF-I and not secondary to increased total RNA or total protein synthesis at the times reported. The effect of insulin on the IGF-I-mediated mesangial cell fibronectin gene expression was also explored. Fibronectin mRNA levels were higher in rnesangial cells treated with IGF-I and insulin than those treated with IGF-I alone. Insulin alone was unable to stimulate fibronectin mRNA synthesis.

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