Synthesis and release of insulinlike growth factor I by mesangial cells in culture

Mesangial cell proliferation is a common hallmark of many glomerular diseases. The exact mechanisms inducing cell proliferation in glomerulosclerosis are not completely understood, and it remains to be determined whether growth factors play a role in this process. Insulinlike growth factor I (IGF I) has been shown to be synthesized in the kidney, and glomerular mesangial cells have receptors for and exhibit mitogenic response to IGF I. We found that mouse glomerular mesangial cells in culture synthesized and released into the culture medium a molecule with immunological and biological features of IGF I. This molecule specifically bound to mesangial cell IGF I receptors; high-pressure liquid chromatographic analysis provided further evidence of its similarity to human recombinant IGF I. Mesangial cells released into the culture medium 6 ng/10(6) cells of IGF I-like material per 24 h in a time-dependent and actinomycin-D inhibitable fashion. These data suggest that IGF I might be locally released by mesangial cells in the glomerulus and act in an autocrine and paracrine fashion.