Regulation of Fibronectin by Insulin-like Growth Factor-I in Cultured Rat Thoracic Aortic Smooth Muscle Cells and Glomerular Mesangial Cells

Abstract

We examined the regulation of fibronectin (FN) levels by insulin-like growth factor-I (IGF-I) in rat thoracic aortic smooth muscle cell (SMC) and glomerular mesangial cell cultures. IGF-I enhances FN levels in the culture media of the SMC and in the cell samples of the mesangial cells. It shows no effect on FN levels in the cell samples of the SMC and in the culture media of the mesangial cells. Modulation of IGF-I-induced FN levels by insulin was also examined. Insulin enhances FN levels in the culture media of the SMC but not in the cell samples. Insulin did not induce an increase in FN levels in either the mesangial cell samples or tile culture media. No additive effect of FN levels was observed when the SMC were treated with insulin and IGF-I together, The effect of IGF-I on FN mRNA levels was assessed, IGF-I enhances SMC and FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. The effects of actinomycin D and cycloheximide on IGF-I-induced FN mRNA levels were also examined. Inhibition of the IGF-I-induced FN mRNA levels by actinomycin D and an increase of FN mRNA levels by cycloheximide suggest that IGF-I regulates FN mRNA synthesis at the transcriptional level.