FIBRONECTIN MODULATES INTERLEUKIN-6 AND FIBRONECTIN SYNTHESIS OF HUMAN GLOMERULAR MESANGIAL CELLS IN CULTURE

In this paper we report that fibronectin (FN) and its proteolytic 120- kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) a nd of FN by human glomerular mesangial cells. While intact FN and a fr agment derived from the heparin-binding domain had no effect on IL-6 s ecretion, the 120-kD FN fragment containing the cell attachment site s timulated secretion by 40-fold. The same FN fragment reduced FN secret ion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/-30%); the 30-kD fragment containing the h eparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell att achment site in signal transduction, tin antibody to the alpha-chain o f VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to t he a-chain of VLA-5 was partly inhibitory. Taken together, the data su ggest that FN by interacting with its receptors differentially regulat es the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.