K Ota

University of Illinois at Chicago, Chicago, Illinois, United States

Are you K Ota?

Claim your profile

Publications (32)172.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy. Purified 1 x 10(4) circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days. The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon alpha-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor. These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.
    American Journal of Kidney Diseases 04/2003; 41(3):624-36. · 5.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mesodermal-specific cDNA or transcript (MEST) was identified by suppression subtractive hybridization-PCR of cDNA isolated from embryonic day 13 vs. newborn mice kidneys. At day 13 of mouse gestation, a high expression of MEST, with a single approximately 2.7-kb transcript that was exclusively localized to the metanephric mesenchyme was observed. The MEST mRNA expression gradually decreased during the later stages and then abruptly decreased in the newborn kidneys and subsequent postnatal life, after which a very mild expression persisted in the glomerular mesangium. Regression in mRNA expression during embryonic renal development appears to be related to methylation of the MEST gene. Treatment of metanephroi, harvested at day 13 of gestation with MEST-specific antisense oligodeoxynucleotide resulted in a dose-dependent decrease in the size of the explants and the nephron population. This was associated with a selective decrease in MEST mRNA expression and accelerated apoptosis of the mesenchyme. These findings suggest that MEST, a gene with a putative mesenchymal cell-derived protein, conceivably plays a role in mammalian metanephric development.
    American journal of physiology. Renal physiology 06/2002; 282(5):F953-65. · 3.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, we have developed a tissue-negative staining method, and successfully visualized fine meshwork structure of the glomerular basement membrane (GBM). To clarify the mechanism of proteinuria in active Heymann nephritis, we performed tissue-negative staining and investigated the ultrastructural alterations of the GBM. Active Heymann nephritis, the animal model of human membranous nephropathy, was induced in Lewis rats by the injection of proximal tubular brush border antigen, i.e. Fx1A. Urinary protein excretion was measured and histological studies were performed over 15 weeks following the Fx1A injection. Proteinuria developed at 10 weeks after injection (38.2 +/- 7.4 mg/day) and progressively increased (160.2 +/- 20.6 mg/day at 15 weeks). Capillary fine deposits of IgG and C3 were seen by immunofluorescence, and subepithelial electron dense deposits (EDD) by transmission electron microscopy (TEM). Using the tissue-negative staining method, regular meshwork structure consisted of fine fibrils and pores (2.5 +/- 0.7 nm in short dimension) was observed in the GBM of control rats. At 10 and 15 weeks after injection, the GBM, directly facing the endothelial side of EDD, contained enlarged pores and nephrotic tunnels. Mean values of the short dimension of enlarged pores were 2.9 +/- 0.5 nm at 10 weeks and 3.1 +/- 0.4 nm at 15 weeks, which were significantly larger than that of control rats (p < 0.01). The rest area of the GBM, including newly produced GBM covering the epithelial side of EDD, had no significant difference in size of the pores from control GBM and no tunnels. Although there was no significant difference in the size of enlarged pores between 10 and 15 weeks, the percentage area of GBM with impaired size barrier increased at 15 weeks (51.4 +/- 8.1%) compared with 10 weeks (24.0 +/- 8.3%) and related to severity of proteinuria. The density of the tunnels also increased at 15 weeks. In conclusion, immune deposits may affect the GBM biosynthesis and induce the defect of size barrier of the GBM, which is responsible for proteinuria in active Heymann nephritis.
    American Journal of Nephrology 01/2001; 21(3):249-55. · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular matrix (ECM) proteins, their integrin receptors, and matrix metalloproteinases (MMPs), the ECM-degrading enzymes, are believed to be involved in various biological processes, including embryogenesis. In the present study, we investigated the role of membrane type MMP, MT-1-MMP, an activator pro-MMP-2, in metanephric development. Also, its relationship with MMP-2 and its inhibitor, TIMP-2, was studied. Since mRNAs of MT-1-MMP and MMP-2 are respectively expressed in the ureteric bud epithelia and mesenchyme, they are ideally suited for juxtacrine/paracrine interactions during renal development. Northern blot analyses revealed a single approximately 4.5-kb mRNA transcript of MT-1-MMP, and its expression was developmentally regulated. Inclusion of MT-1-MMP antisense oligodeoxynucleotide (ODN) in the culture media induced dysmorphogenetic changes in the embryonic metanephros. MMP-2 antisense ODN also induced similar changes, but they were relatively less; on the other hand TIMP-2 antisense ODN induced a mild increase in the size of explants. Concomitant exposure of MT-1-MMP and MMP-2 antisense ODNs induced profound alterations in the metanephroi. Treatment of TIMP-2 antisense ODN to metanephroi exposed to MT-1-MMP/MMP-2 antisense notably restored the morphology of the explants. Specificity of the MT-1-MMP antisense ODN was reflected in the selective decrease in its mRNA and protein expression. The MT-1-MMP antisense ODN also resulted in a failure in the activation of pro-MMP-2 to MMP-2. These findings suggest that the trimacromolecular complex of MT-1-MMP:MMP-2:TIMP-2 modulates the organogenesis of the metanephros, conceivably by mediating paracrine/juxtacrine epithelial:mesenchymal interactions.
    The American journal of physiology 01/2000; 277(6 Pt 2):F934-47. · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alphavbeta3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had approximately 88% homology with human fibrillin-2 and had Ca(2+) binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an approximately 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alphav and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.
    Developmental Biology 09/1999; 212(1):229-42. · 3.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glomerular basement membranes (GBM) and tubular basement membranes (TBM) consist of a fine meshwork composed mainly of type IV collagen. Each segment of tubules has specialized physiologic functions, and thus we investigated the ultrastructure of various basement membranes in rat kidneys. Since purifying basement membranes from different tubule segments is technically challenging, we employed tissue negative staining rather than conventional negative staining to compare the ultrastructures of proximal and distal TBM and GBM in normal rats. We also assessed the distribution of extracellular matrix components including type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basement membranes by immunohistochemistry. TBM and GBM of normal rats showed a fine meshwork structure consisting of fibrils forming small round to oval pores. Short- and long-pore diameters in proximal tubules were 3.3 +/- 0.5 and 3.9 +/- 0.6 nm, respectively, and in distal tubules 3.5 +/- 0.7 and 4.3 +/- 0.8 nm, respectively. For GBM the respective diameters were 2.5 +/- 0.5 and 3.0 +/- 0.5 nm. Immunohistochemical analysis showed no significant difference in distribution of extracellular matrix components between proximal and distal TBM. However, immunofluorescence scores of alpha1 chain of type IV collagen, fibronectin, and laminin were higher in the TBM than in the GBM. On the other hand, heparan sulfate proteoglycan was higher in the GBM. Ultrastructural differences in renal basement membranes may be related to differences in physiologic function in each segment.
    American Journal of Nephrology 02/1999; 19(6):686-93. · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied. It had approximately 88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and an RGD binding site. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-1 expression was developmentally regulated. In situ hybridization and immunofluorescence studies indicated that at day 15 of gestation, fibrillin-1 is expressed in the metanephric mesenchyme. At day 18, its expression was confined to nascent blood vessels and glomeruli, and it increased in the newborn and neonatal kidneys. Immunoprecipitation revealed an approximately 300-kDa band by SDS-PAGE. Treatment with fibrillin-1 antisense oligodeoxynucleotide induced marked dysmorphogenesis of the embryonic metanephroi. Concomitantly, the fibrillin-1 mRNA, antibody reactivity in the metanephroi, and fibrillin-1-specific radioincorporation were reduced. These data indicate that, like alphavbeta3 integrin, a known morphogen and a putative receptor of fibrillin-1, the fibrillin-1 modulates events related to early organogenesis and possibly also the vascularization of the rat kidney.
    The American journal of physiology 12/1998; 275(5 Pt 2):F710-23. · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of IgA nephropathy with focal and segmental deposition of type III collagen in mesangium, confirmed by immunohistochemical and electron microscopic methods. Tissue negative staining showed that focal and segmental fibrotic lesions in the mesangial area consisted of disarrayed or curled striated collagen fibers and striated membranous structures. Diabetes mellitus, hypertension, and advanced glomerular sclerosis were absent in this case, and mesangial cells surrounding the type III collagen showed vacuolar degeneration revealed by electron microscopy. Production of type III collagen may be the marker for phenotypic change of mesangial cells in immune-mediated glomerular diseases.
    American Journal of Kidney Diseases 08/1998; 32(1):146-52. · 5.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular matrix macromolecules regulate morphogenesis of embryonic organs, and are developmentally regulated. Their expression and turnover is regulated by matrix metalloproteinases (MMPs). Recently, an epithelial cell "membrane" associated metalloproteinase (MT-1-MMP) has been identified that acts as an activator of a "secreted" MMP-2, and is produced by mesenchymal fibroblasts. The activity of MMP-2 is inhibited by a "soluble" tissue inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown. MT-1-MMP was cloned from embryonic mouse kidney cDNA library, and its spatio-temporal distribution during development in the context of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was studied. The cloned MT-1-MMP exhibited approximately 86% nucleotide sequence homology with human MT-1-MMP, and had a catalytic domain and a zinc binding site preceded by a RRKR furin recognition motif. A approximately 4.5 Kb MT-1-MMP mRNA transcript was detected, and its expression was developmentally regulated. A parallel developmental regulation of MMP-2 mRNA expression was also observed. TIMP-2 expression was also developmentally regulated, but lagged behind MT-1-MMP and MMP-2. By in situ hybridization, MT-1-MMP mRNA was seen to be confined to ureteric bud epithelia, and was absent in the mesenchyme, while MMP-2 was confined to the mesenchyme. MT-1-MMP protein expression was seen on ureteric bud epithelia, induced mesenchyme and nascent nephrons, and it was highest during mid gestation. Similar spatio-temporal expressions of MMP-2 and TIMP-2 proteins were observed. mRNAs of MT-MMP-1 and MMP-2 are expressed in the respective epithelial and mesenchymal compartments, while their proteins are co-expressed in the epithelia suggest that MT-1-MMP and MMP-2, in conjunction with TIMP-2, may be involved in paracrine/juxtacrine epithelial:mesenchymal interactions during metanephrogenesis.
    Kidney International 08/1998; 54(1):131-42. · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor.Background Extracellular matrix macromolecules regulate morphogenesis of embryonic organs, and are developmentally regulated. Their expression and turnover is regulated by matrix metalloproteinases (MMPs). Recently, an epithelial cell "membrane" associated metalloproteinase (MT-1-MMP) has been identified that acts as an activator of a "secreted" MMP-2, and is produced by mesenchymal fibroblasts. The activity of MMP-2 is inhibited by a "soluble" tissue inhibitor of MMP-2, TIMP-2. The role of MT-1-MMP in renal development is unknown.
    Kidney International 06/1998; 54(1):131-142. · 8.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We previously reported in Nephron that the hematuria observed in patients with glomerulonephritis was caused by a rupture of the glomerular basement membrane [1], a layer that had the strongest resistance to stretching among three layers within the cylindrical capillary wall, and had a three-dimensional meshwork structure composed of fine pores and fibrils and having an isotropic property [2, 3]. Using scanning electron microscopy, we noticed that the split lines caused by the ruptures of the glomerular basement membranes were almost always linear in shape and that they were frequently parallel to the axis of the capillary. This phenomenon can be explained by the elastodynamic theory [4], as follows.
    Nephron 02/1998; 79(3):345-7. · 13.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Developmental regulation and partial-length cloning of tubulointerstitial nephritis antigen of murine metanephros. Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix (ECM) glycoprotein that has been recently isolated and cloned from the rabbit kidney. It is an integral component of the basal lamina, and unlike other basement membrane proteins it is exclusively expressed in the tubular basement membranes (TBMs). Since other ECM glycoproteins have been shown to regulate development of various organ systems, studies were initiated to ascertain its developmental regulation in renal tubulogenesis and glomerulogenesis. Embryonic (day-13 and -17 of gestation), newborn and one-week-old mice kidneys were harvested for expression of TIN-ag as well as cDNA cloning studies. Immunostaining with polyclonal anti-TIN-ag antibody revealed its localization to the basal lamina of ureteric bud branches and epithelial elements of developing nephrons in day-13 embryonic kidneys. Interestingly, it was heavily expressed at the tips of the ureteric bud branches, and was not expressed in the distal convolutions of the S-shaped body stage of the nephrons, the region which forms the future glomerulus. At day-17, TIN-ag expression was less, and the immuno-reactivity was mainly localized to the cortex. In the newborn and one-week-old mice kidneys, the cortical expression of TIN-ag increased progressively, but was absent in the glomeruli. The TIN-ag expression was confined to the cortical TBMs, while absent in the medullary tubules, the latter included segments of the collecting ducts and loop of Henle. Immunoprecipitation studies on [35S]methionine-labeled metanephroi revealed a single band of ~58 kDa at day-13, and the incorporated radioactivity decreased at day-17. No high molecular weight isoforms were observed. A partial-length mouse TIN-ag cDNA of ~530 bp PCR product was generated, and it had ~88% and ~93% nucleotide and amino acid sequence homolgy, respectively, with rabbit TIN-ag. Utilizing this cDNA, Northern blot analyses revealed a single transcript of ~2 Kb in fetal and postnatal mice kidneys. mRNA expression initially decreased at day-17, and then progressively increased by one week. Utilizing a mouse TIN-ag riboprobe, in situ hybridization studies revealed a generalized diffuse expression of TIN-ag in the epithelial elements of developing nephrons and ureteric bud branches at day-13. Gene expression decreased by day-17, and became confined to the renal cortex, and then progressively increased during the neo- and post-natal periods, but remained absent in the renal medulla and glomeruli. These data indicate that TIN-ag is expressed in the metanephros early in embryonic life in the absence of any detectable isoforms, and it exhibits spatio-temporal characteristics during metanephric development. Being concentrated at the tips of the ureteric bud branches, it is conceivably involved in epitheliahmesenchymal interactions which are highly prevalent during renal organogenesis, and its role in tubulogenesis diverges from glomerulogenesis at the S-shaped body stage of the nephron.Keywords: tubulointerstitial nephritis antigen, renal development, extracellular matrix, cloning, murine metanephros
    Kidney International 10/1997; 52(3). · 8.52 Impact Factor
  • Kidney International 10/1997; 52(3). · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The insulin family of peptides and their receptors influence cellular growth in very early preimplantation embryos. In this study their expression and role in renal organogenesis was investigated. By immunofluorescence microscopy and in situ hybridization, insulin receptor (IR) expression was seen in the ureteric bud branches and early nephron precursors in mouse metanephroi harvested at day 13 of gestation. The expression gradually decreased in successive stages of gestation, and it was confined mainly to renal tubules in 1-week-old mice. Similar developmental regulation of the IR and insulin was observed by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Addition of insulin into the culture medium at low concentrations, ranging from 40 to 400 ng/ml, induced trophic changes and increased [3H]thymidine incorporation in the embryonic renal explants, and inclusion of IR beta-subunit-specific antisense oligodeoxynucleotide caused marked dysmorphogenesis and growth retardation of the metanephroi. Specificity of the antisense effect was reflected by immunoprecipitation experiments in which translational blockade of the beta subunit of the IR was observed. RT-PCR analyses revealed that the alpha subunit of the IR was unaffected by the antisense treatment of metanephric explants. Concomitantly, de novo synthesis of morphogenetic regulatory extracellular matrix proteins, especially the proteoglycans, was decreased. Gel-shift analyses indicated a failure in the activation of c-fos promoter region binding protein(s) by insulin in the antisense oligodeoxynucleotide-treated explants. These studies suggest that insulin and its putative receptor are developmentally regulated in the murine embryonic metanephros, and they play a role in renal organogenesis, possibly by affecting other modulators of morphogenesis-i.e., extracellular matrix proteins and protooncogenes.
    Proceedings of the National Academy of Sciences 07/1997; 94(13):6758-63. · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based differential cloning method. It involves hybridization of two populations of cDNA with selective amplification of differentially expressed genes. To isolate the differentially expressed genes during renal development, mRNAs from embryonic kidneys at day 13 (E13) and postnatal kidneys from three-week-old (P3) mice were extracted, and double stranded cDNAs prepared. Double stranded cDNAs were digested with DpnII, adaptor-ligated, and amplified by PCR, using adaptor primer to generate "representative amplicons." These reflect the "representation" of most of the cDNA population. The term "amplicons" denotes amplified PCR product. Among the two populations of cDNA, E13 kidney cDNA was used as a "tester," containing target genes, and P3 kidney cDNA as a "driver," driving the process of subtraction, following which, they were subjected to cDNA-RDA under low stringency conditions. During the first round of cDNA-RDA embryonic globin genes were isolated. To competitively eliminate these genes, plasmid DNAs of globin genes were supplemented into driver, and subjected to the second round of cDNA-RDA. This resulted in the isolation of four cDNA clones: H19 gene, mesoderm-specific cDNA, COL2A1 gene, and a novel cDNA. By Northern blot analyses, the H19 gene and mesoderm-specific cDNA exhibited a high degree of developmental regulation, that is, they were abundantly expressed in E13 kidney, and their expression was barely detectable in P3 kidney. The differential developmental regulation of mesoderm-specific cDNA was confirmed by tissue in situ hybridization experiments. The COL2A1 and novel cDNA were rare transcripts in the embryonic Kidney. However, Southern blot analyses of representations indicated their up-regulated expressions in E13 kidneys. The novel gene was differentially expressed in 13-day embryonic lung, and Northern blot analysis revealed an approximately 10 Kb transcript. These results indicate that cDNA-RDA is a sensitive technique to identify rare transcripts with differential expression, and since there is a minimal chance to isolate false positive clones, cDNA-RDA may serve as a powerful tool for delineating up- or down-regulation of the genes involved in various pathological or physiological states of the kidney.
    Kidney International 06/1997; 51(5):1629-38. · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 microM concentration, induced apoptosis in approximately 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed approximately 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus.
    Journal of Clinical Investigation 06/1997; 99(10):2452-61. · 12.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Platelet-derived growth factor (PDGF) is an important mitogenic factor for various cells. In order to elucidate the role of PDGF in the development of human glomerulonephritis, we examined the gene and protein expression of the PDGF-B chain (PDGF-B) and PDGF-beta receptor (PDGFR-beta) in renal biopsy specimens from patients with various forms of glomerulonephritis using a nonradioactive in situ hybridization and an immunohistochemical technique. The mRNA expression of PDGF-B and PDGFR-beta was significantly increased in the glomeruli of patients with mesangial proliferative glomerulonephritis (IgA nephropathy, Henoch-Schönlein purpura nephritis, and lupus nephritis) compared with those in normal glomeruli. In cases with increased protein expression of PDGF-B and PDGFR-beta, each mRNA expression was also increased. The degree of glomerular injury was positively correlated with the number of mRNA-positive cells for both PDGF and PDGF receptor. There was also a positive correlation between the number of mRNA-positive cells for PDGF-B and PDGFR-beta. PDGF-B and PDGFR-beta were also expressed on cells of the capillary wall, cellular crescents and infiltrated cells in the interstitium. The results suggest that PDGF acts as an important and common mediator for the development of various forms of human mesangial proliferative glomerulonephritis. Furthermore, PDGF may participate in crescent formation and tubulo-interstitial injury.
    American Journal of Nephrology 02/1997; 17(1):25-31. · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD11a/CD18), Mac-1 (CD11b/CD18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.
    Nephron 02/1996; 73(2):264-72. · 13.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal hypertrophy is a characteristic and early manifestation of diabetes in humans and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. No significant difference in the distribution of IGF-I mRNA was found between the diabetic and control rats. IGF-I mRNA-positive cells were found in the collecting ducts and in scattered single cells in the distal tubules. The number of IGF-I mRNA-positive cells was very low in the glomeruli. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly, peaking at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells, especially mesangial and visceral epithelial cells, may contribute to glomerular hypertrophy in diabetic nephropathy.
    Nephron 02/1996; 72(4):648-53. · 13.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 10-year-old boy presented in 1989 with repeated episodes of vomiting, abdominal distension and severe growth retardation. Endocrinologic examination indicated growth hormone (GH) secretory dysfunction. Administration of recombinant human GH (rhGH) led to growth, but the patient discontinued treatment. He was readmitted to our hospital in 1993, at the age of 16. His stature was very short. Laboratory findings suggested malnutrition. Radiologic examination revealed regional stenosis and a cobblestone appearance of the intestine. The histologic diagnosis was compatible with Crohn's disease. Administration of prednisolone alleviated gastrointestinal symptoms with the improvement of GH secretory function.
    Internal Medicine 03/1995; 34(2):112-7. · 0.97 Impact Factor