Nishizawa Y, Fukai F, Natori Y, Katayama T
Department of Patho-Physiology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Biol Pharm Bull. 1998 May;21(5):429-33. doi: 10.1248/bpb.21.429.
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.
采用酶免疫测定和免疫印迹分析方法，研究了正常大鼠和被动型海曼肾炎（PHN）大鼠尿液中纤连蛋白（FN）相关物质的排泄机制。在正常大鼠中，由源自FN中央细胞结合（Cell）结构域的55 kDa和65 kDa FN片段组成的少量（0.20±0.067 μg/d）FN相关物质持续排泄到尿液中。当通过注射抗Fx1A抗体诱导大鼠发生PHN时，观察到完整FN和包含Cell及其他功能结构域的大（Mr>100 kDa）FN片段的排泄增加（4.96±3.51 μg/d）。PHN诱导还导致血浆中出现大量含Cell结构域的FN片段。正常大鼠和PHN大鼠的肾皮质匀浆均能够降解血浆FN以生成含Cell结构域的大FN片段。肾皮质匀浆对FN的降解被证明是由于金属和/或巯基蛋白酶。这些结果表明，PHN诱导的FN片段尿排泄可能是由于肾蛋白酶对血浆FN的降解，而肾蛋白酶可能在PHN诱导时泄漏。
