Accession Number : AD1011295


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


Descriptive Note : Technical Report


Corporate Author : Uniformed Services University Of The Health Sciences Bethesda United States


Personal Author(s) : Tamaroglio,Terry


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1011295.pdf


Report Date : 21 Sep 1993


Pagination or Media Count : 128


Abstract : 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 ng/ml 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.


Descriptors :   gene expression , cells (biology) , rats , Vascular diseases , diabetes , cell physiological processes , Glycoproteins , tissues (biology) , deoxyribonucleic acids , ribonucleic acids , Insulin


Distribution Statement : APPROVED FOR PUBLIC RELEASE