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Accumulation of CD8 + lymphocytes and Mƒ³ in glomeruli occurs in WRY rats after anti-gbm antibody administration. However, a role of the antibody in the leukocyte accumulation is unclear.

20 Accumulation of CD8 + lymphocytes and Mƒ³ in glomeruli occurs in WRY rats after anti-gbm antibody administration. However, a role of the antibody in the leukocyte accumulation is unclear. An involvement of Fc portion of the IgG antibody in the initiation was examined in the present studyby injecting with intact IgG antibody (15mg/ kg body weight) or its F (ab') 2 fragment (0.75mg/kg=equivalent moles). Although binding of both IgG and F (ab') 2 of the anti-gbm antibody to GBM was identical by immunofluorescence microscopy, the anti GBM glomerulonephritis was induced only in the animals injected with the intact IgG antibody as judged by accumulation of CD8 + lymphocytes and M, incidence of crescent formation, and excretion of urinary protein (142 }25 vs 7 2mg//day, p<0.01) at day 10. No significant proteinuria, glomerular accumulation of M and crescent fromation were observed in the F (ab') 2 antibody-injected rats. Expression of mrna for Fe y receptor 2 and 3 was intense and that for Fe y receptor 1 was faint in the glomeruli of the intact IgG antibody-injected rats, but those were faint or negligible in rats injected with the F (ab') 2 fraction of anti-gbm antibody at day 10. Complement depletion by pretreatment with cobra venom factor did not effect on induction of this model. These results suggest that interaction between Fe portion of the anti- (IBM antibody and Fe y receptors on infiltrating leukocytes may initiate induction of this glomerulonephritis model.

22 Ets-1 is a proto-oncogene, act as a transcription factor of extracellular matrix degradaing proteases. In response to external stimuli,transcription factors may increase or decrease related gene products. To clarify the role of cisplatin on ets-1, cisplatin nephropathy induced inmale Wister rats (n = 20). Nephrotoxicit y developed initial severe tubular damage fol lowed by accessive extracellular matrix accumulation around them. Expression of ets-1 determined by in situ hybridization and immunohisto chemistry. Lowered immunohistoehenneal expression of ets-1 andmatrix metalloproteinase 3 followed by increased collagen type V deposition. In conclusion, cisplatin might be related with suppression of ets-1 in expreimental model in rat. To clarify the effect of diet restriction on immunohistochemical expression of HSP47, morphological and immunohistochemical analysis done on a group of obese Zucker rats, those develop spontaneous focal segmental glomerulosclerosis (FGS). Diet restricted obese Zucker rats showed less renal damages both in glomeruli and tubulointerstitium. Obese Zucker rats developed 54%, while diet restricted obese Zucker rats 43% and lean control 23% of FGS. Increased expression of HSP47 seen in and around FGS and damaged tubulointerstitium. In conclusion, diet restriction lower renal damages and inhibit increase expression of HSP47 in obese Zucker rats.

The transcription factor NF- K B is activated at the site of renal inflammation and plays a critical role in the expression of immune and inflammatory genes.

28 The transcription factor NF- K B is activated at the site of renal inflammation and plays a critical role in the expression of immune and inflammatory genes. Using the yeast two hybrid screening, we searched for protein molecules which physically interact with the p65 (Re1A) subunit of NF - K B. We have identified RNA helicase A (RHA) as an interacting molecule with p65. RHA is a component of the RNA polymerase U holoenzyme complex. It has been reported that RHA directly binds to the coactivator, CREB-binding protein (CBP), and the tumor suppressor protein, BRCAl, and links them to RNA polymerase U holoenzyme complex. The interaction between p65 and RHA was confirmed by GST pull-down assay in vitro, and by co-immunoprecipitation assay in vivo. In transient transfection assays, RHA enhanced NF- K B dependent reporter gene expression induced by p65, TNFa, or NIK (NF- K B inducing kinase). The mutant form of RHA lacking ATP-binding activity inhibited NF- K B dependent reporter gene expression induced by these activators. These data suggest that RHA acts as a coactivator for NF- k B and that RHA may play a pivotal role in regulation of NF- k B target genes.

Background : It is not known whether tissue factor (TF), an important initiator of extrinsic coagulation cascade, is increased in diabetes mellitus.

29 Background : It is not known whether tissue factor (TF), an important initiator of extrinsic coagulation cascade, is increased in diabetes mellitus. We examined TF expression in the kidney of streptozotocin (STZ) -induced diabetic rats.methods : SD rats were divided into three groups : Group 1 (G-1) diabetic rats, Group 2 (G-2) : diabetic rats with well controlled blood sugar (BS) using insulin, Group 3 (G-3) : normal rats. Rats were sacrificed at 21 days after induction of diabetes. TF expression in kidney tissue was examined by immunohistochemical method and the area stained was compared by IBAS system. Prothrombin time (PT) was measured also. Results : BS (mg/ dl) in GI (578 } 13) showed significantly higher than those in G2 (89 } 13) and G3 (111 } 5). The percent area of TF stained in glomeruli were significantly larger in G-1 (18.9 } 1.0) than those in G-2 (11.3 }0.4) and G3 (12.0 } 1.5), whereas there was no difference of the number of tubules with TF stained among three groups. PT (sec) was significantly shorten in G1 (10.9 } 0.1) than those in G2 (12.3 } 0.3) and G3 (11.8 } 0.2). Conclusions Intraglomerular coagulation and systemic hypercoagulable state might be induced with hyperglycemia in STZ-induced diabetic SD rats.

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