Characterization of fibronectin-related substances in normal and passive Heymann nephritis rats.

Abstract

The excretion mechanism of fibronectin (FN)-related substances into the urine of normal and passive Heymann nephritis (PHN) rats was studied using enzyme immunoassay and immunoblot analysis. In normal rats, a small amount (0.20+/-0.067 microg/d) of FN-related substances, composed of 55- and 65-kDa FN fragments derived from the central cell-binding (Cell) domain of FN, were constitutively excreted into the urine. When PHN was induced in rats by the injection of an anti-Fx1A antibody, an increased excretion (4.96+/-3.51 microg/d) of intact FN and large (Mr > 100-kDa) FN fragments containing the Cell and the other functional domains were seen. The PHN induction also caused the appearance of a considerable amount of Cell domain-containing FN fragments in plasma. Both the renal cortex homogenates of normal and PHN rats were capable of degrading plasma FN to generate the Cell domain-containing large FN fragments. Degradation of FN by the renal cortex homogenate was shown to be due to metal and/or thiol proteinase(s). These results suggest that the PHN-induced urinary excretion of FN fragments may be due to the degradation of plasma FN by renal proteinases that may be leaked upon PHN induction.