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S Kagami

Publications and source records attributed to S Kagami.

At least 19 recordsLinked to original sources
PubMed1999

Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factor-beta and platelet-derived growth factor-BB.

Pathologic remodeling of mesangial matrix after glomerular injury is the central biologic feature of glomerular scarring (sclerosis). Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated in the development of glomerular scarring in rat and human glomerulonephritis. To clarify molecular and cellular mechanisms involved in abnormal mesangial remodeling, this study focused on the role of alpha1beta1 integrin, a collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction as an experimental model of in vivo collagen matrix remodeling and scar formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell (MC)-mediated collagen gel contraction in association with the alpha1beta1 integrin expression was evaluated. Integrin function blocking studies using anti-alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is essentially required not only for collagen-dependent adhesion/migration, but also for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin in mesangial cells cultured on plastic surface and in collagen gels. The upregulation of alpha1beta1 integrin expression by TGF-beta correlated with increases in gel contraction and collagen-dependent adhesion but not migration of mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction and migration without affecting cell adhesion to collagen I. Growth factor-induced collagen-dependent adhesion, migration, and gel contraction were significantly attenuated by incubation with anti-alpha1, beta1 subunit antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen matrix remodeling can be modulated by TGF-beta and PDGF-BB via different mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF-beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.

Animals↗
PubMed1998

Collagen type I modulates the platelet-derived growth factor (PDGF) regulation of the growth and expression of beta1 integrins by rat mesangial cells.

Mesangial cell (MC) proliferation and the deposition of collagen type I (collagen I) are the major pathological features in many types of glomerulonephritis (GN). Recent work suggested that beta-integrins play a critical role in the cell proliferation and extracellular matrix (ECM) remodeling observed in tissue repair after injury. To examine the involvement of beta-integrins in MC proliferation in association with the interaction of MCs with pathological collagen I, we investigated the effect of a prominent mitogen, platelet-derived growth factor-BB (PDGF-BB) on the growth and expression of beta-integrins by MCs cultured on plastic or in a three-dimensional collagen I gel. Immunoprecipitation using 35S-metabolic labeling, flow cytometry and a 3H-thymidine-uptake analysis demonstrated that PDGF-BB stimulated the cell mitogenicity and the expression of alpha5beta1 integrin (a fibronectin receptor), but not alpha1beta1 integrin (a collagen and laminin receptor) of MCs on plastic, in a dose-dependent manner. In contrast, MCs in the collagen I gels showed no significant changes in mitogenicity or alpha1beta1 and alpha5beta1 integrin expression, but increased alpha1beta1 integrin-mediated gel contraction was observed after PDGF-BB stimulation. Thus, the parallel up-regulation of MC-mitogenicity and alpha5beta1 integrin expression by PDGF-BB suggested that alpha5beta1 integrin is an important ECM receptor involved in the proliferative phenotype of MC. A spatial interaction between MCs and pathological collagen I in GN may influence the PDGF regulation of the MC phenotype regarding the cell growth and the expression of beta1 integrins.

Animals↗
PubMed1998

Effect of endothelin-1 (1-31) on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells.

1. We have previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31), without any further degradation products. In this study, we investigated the effect of synthetic ET-1 (1-31) on the proliferation of cultured human coronary artery smooth muscle cells (HCASMCs). 2. ET-1 (1-31) increased [3H]-thymidine incorporation and cell numbers to a similar extent as ET-1 at 100 nM. This ET-1 (1-31)-induced [3H]-thymidine uptake was not affected by phosphoramidon, an inhibitor of ET-converting enzyme. It was, however, inhibited by BQ123, an endothelin ET(A) receptor antagonist, but not by BQ788, an endothelin ET(B) receptor antagonist. 3. By using an in-gel kinase assay, we demonstrated that ET-1 (1-31) activated extracellular signal-regulated kinase 1/2 (ERK1/2) in a concentration-dependent manner (100 pM to 1 microM) in HCASMCs. ET-1 (1-31)-induced ERK1/2 activation was inhibited by BQ123, but not by BQ788 and phosphoramidon. Inhibition of protein kinase C (PKC) and ERK kinase also caused a reduction of ET-1 (1-31)-induced ERK1/2 activation, whereas tyrosine kinase inhibition had little effect. 4. Gel-mobility shift analysis revealed that the ERK1/2 activation was followed by an increase in transcription factor activator protein-1 DNA binding activity in HCASMCs. 5. Our results strongly suggest that ET-1 (1-31) itself stimulates HCASMC proliferation probably through endothelin ET(A) or ET(A)-like receptors. The underlining mechanism of cell growth by ET-1 (1-31) may be explained in part by PKC-dependent ERK1/2 activation. Since human chymase has been proposed to play a role in atherosclerosis, ET-1 (1-31) may be one of the mediators.

Arteries↗
PubMed1998

Selective inhibition of the bacterial peptidoglycan biosynthesis by the new types of liposidomycins.

We examined the inhibitory activity against bacterial peptidoglycan biosynthesis, mammalian glycoprotein biosynthesis and growth of BALB/3T3 cells of four different types of liposidomycins which have the structure with or without sulfate and/or 3-methylglutaric acid moieties. Liposidomycins inhibited peptidoglycan biosynthesis about 30 to 500 times more effectively than tunicamycin, whereas liposidomycins inhibited mammalian glycoprotein biosynthesis about 30 to 300 times less effectively than tunicamycin. When the cytotoxic effect of liposidomycins and tunicamycin on the growth of mammalian cells were compared, liposidomycins did not show toxicity against BALB/3T3 cell at 25 microg/ml, though tunicamycin inhibited cell growth by 50% at 0.05 microg/ml. On the basis of these results, it is concluded that liposidomycins are selective antibiotics showing highly specific inhibition toward bacterial peptidoglycan biosynthesis.

3T3 Cells↗
PubMed1998

New types of liposidomycins that inhibit bacterial peptidoglycan synthesis and are produced by Streptomyces. I. Producing organism and medium components.

Liposidomycins are atypical lipid-bearing nucleoside antibiotics that inhibit bacterial peptidoglycan synthesis. A producing strain was identified as a Streptomyces sp. from its cultural characteristics and physiological properties. It produced new types of liposidomycins that lacked sulfate and/or 3-methylglutaric acid moieties present in known liposidomycins by changing medium components. Sucrose and malt extract were particularly suitable sources for specific production of the new types of liposidomycins.

Aminoglycosides↗
PubMed1998

New types of liposidomycins that inhibit bacterial peptidoglycan synthesis and are produced by Streptomyces. II. Isolation and structure elucidation.

Various new liposidomycins were isolated from a culture of the strain Streptomyces sp. SN-1061M by changing medium components and they were classified into four types (I-IV) based on their structures. They were purified by butanol extraction, silica gel and LH-20 column chromatographies, and high performance liquid chromatography on ODS columns. Type (I) has the original structure which has sulfate and 3-methylglutaric acid moieties. Type (II) has no 3-methylglutaric acid moiety and type (III) has no sulfate moiety. Type (IV) has neither moiety. Type (III) and (IV) compounds, which have no sulfate moiety, exhibited more potent antimicrobial activity.

Aminoglycosides↗
PubMed1997

Dual effects of angiotensin II on the plasminogen/plasmin system in rat mesangial cells.

Previous studies indicate that angiotensin II (Ang II) stimulates extracellular matrix synthesis through induction of transforming growth factor-beta (TGF-beta) expression. Here we investigate Ang II effects on the plasmin protease system. Plasmin both degrades extracellular matrix itself and activates metalloproteinases which then degrade collagens. Plasmin production is determined by the balance between plasminogen activators (PA) and their inhibitors (PAI-1,2). The data presented here indicate that Ang II treatment of mesangial cells in culture markedly increases PAI-1 gene transcription and PAI-1 mRNA levels but does not change the half life of PAI-1 mRNA. Increased PAI-1 protein was detected 24 hours after Ang II stimulation with a concomitant decrease of PA activity. To determine whether these effects were mediated by TGF-beta, cells were coincubated with Ang II and neutralizing antibody to TGF-beta. Induction of PAI-1 at four hours was not altered but the prolonged effect of Ang II on PAI-1 protein synthesis was markedly diminished. Thus, Ang II acts both through rapid, direct transcriptional up-regulation of the PAI-1 gene and through induction of TGF-beta, providing sustained changes in the PAI-1/PA system, which would favor extracellular matrix accumulation by inhibiting turnover. These data provide further evidence that Ang II can act as a potent fibrogenic molecule independent of its effects on blood pressure.

Angiotensin II↗
PubMed1997

A monoclonal antibody (1F3) to human glomerular epithelial cells: a new marker for renal epithelial cell injury.

In order to identify a new cell surface antigen as a potential marker of renal epithelial cell injury, we produced a monoclonal antibody (Mab), 1F3, by immunizing mice with cultured human glomerular cells. Immunofluorescence (IF) and immunoelectron microscopy (IEM) studies demonstrated that 1F3-recognizing antigen (1F3 antigen) was strongly expressed on the cell surface of glomerular podocytes and very weakly on parietal epithelial cells. 1F3 antigen was not expressed in any other cells in the normal kidney. Immunoprecipitation analysis using metabolically labeled glomeruli revealed that 1F3 recognized a 125-kD protein under reducing conditions. IF studies of biopsy specimens from patients with a variety of glomerular and tubulointerstitial diseases showed that 1F3 antigen was almost negative in cellular crescents but was strongly expressed in fibrocellular crescents. When glomerular sclerosis appeared, the expression of 1F3 antigen decreased in sclerotic areas of glomeruli. 1F3 antigen became positive in atrophic tubules that were seen in diseased kidneys. Severity of tubular atrophy correlated well with the extent of tubular expression of 1F3 antigen. These results indicate that Mab, 1F3 marks phenotypic changes of renal epithelial cells under disease conditions and may be a useful marker for progressive kidney diseases.

Animals↗
PubMed1997

Expression of beta 1-integrins on activated mesangial cells in human glomerulonephritis.

beta 1-integrins, a family of cell-surface receptors, mediate cell-matrix interactions that play a critical role in tissue development and tissue remodeling after injury. In this study, to clarify the importance of beta 1-integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of beta 1-integrins, their ligand matrix components, alpha-smooth muscle actin (alpha-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-beta (TGF-beta), and glomerular cellularity in two normal kidneys, ten minimal change nephrotic syndrome, 23 immunoglobulin A (IgA) GN, 13 lupus GN, and four membranous GN kidneys were studied. Immunostaining was performed on frozen sections, using monoclonal anti-alpha-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of alpha 1 beta 1 (collagen/laminin receptor), alpha 5 beta 1 (fibronectin receptor) and TGF-beta. Quantitation of staining indicated that the glomerular expression of alpha 1 beta 1 and alpha 5 beta 1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), alpha-SM actin (P < 0.01), and TGF-beta (P < 0.01). In addition, a correlation was observed between an increased expression of alpha 1 beta 1 and alpha 5 beta 1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing alpha-SM actin strongly expressed alpha 1 beta 1 and alpha 5 beta 1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-beta staining (P < 0.01). In conclusion, enhanced expression of beta 1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-beta appears to be involved in these MC phenotypic changes.

Actins↗
PubMed1996

Transforming growth factor-beta (TGF-beta) stimulates the expression of beta1 integrins and adhesion by rat mesangial cells.

Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of mesangial matrix (MM) accumulation in human and experimental glomerulonephritis. To clarify molecular mechanisms responsible for pathological MM deposition, we examined the effect of TGF-beta on the production of beta1 integrins and on adhesion function of rat mesangial cells (MC). In immunoprecipitation experiments using [35S]methionine-labeled MC, stimulation of MC with TGF-beta for 48 h resulted in an increase in the synthesis of alpha1beta1 (collagen/laminin receptor) and alpha5beta1 (fibronectin receptor) integrins accompanied by increases in the synthesis of their ligands, collagen type I (collagen I), and fibronectin. A time-dependent increase in beta1, alpha1 integrin subunit mRNA peaking 48 h after exposure to TGF-beta was shown by Northern blot analysis. After 48 h of treatment with TGF-beta, MC displayed significant increases in adhesion to fibronectin, collagen I, and laminin as compared to untreated MC. Anti-beta1 antiserum significantly inhibits MC adhesion to fibronectin, collagen I, and laminin. Anti-alpha1 subunit antibody very strongly inhibited adhesion to collagen I and laminin, but not to fibronectin. Synthetic peptides containing RGD sequences specifically blocked adhesion to fibronectin. These data suggest that TGF-beta may promote MM deposition by increasing MC synthesis of both matrix proteins and beta1 integrins which facilitate binding of these proteins to the MC surface and thus enhance their incorporation into MM.

Animals↗
PubMed1996

Establishment and characterization of two cultured cell lines derived from malignant rhabdoid tumors of the kidney.

Malignant rhabdoid tumor of the kidney (RTK) is a rare renal sarcoma of childhood. Its histogenesis is unclear, and it is highly resistant to multimodality therapy. To elucidate the origin and the oncogenetic potential of RTK, we investigated the characteristics of 2 newly established RTK cell lines, SWT-1 and SWT-2. Both cell lines were verified to be RTK, since they did not exhibit contact inhibition and exhibited intermediate filaments, a specific marker for RTK. These cells possess the characteristics of mesenchymal cells based on their positive reactions with anti-vimentin and anti-laminin antibodies and their negative reactions with anti-keratin and anti-desmin antibodies. The karyotype of SWT-1 was 46,XX and that of SWT-2 was 46,XX,del(11)(pter-p13::p12-qter). Since 11p13 is the location of the WT-1 tumor-suppressor gene, and del(11p13) is associated with the aniridia-Wilms'-tumor syndrome, these findings link RTK with Wilms' tumor. While SWT-1 was negative for the tumor markers examined, SWT-2 released tissue polypeptide antigen into the culture supernatant. No rearrangement or amplification of the myc and ras oncogenes or of the p53 tumor-suppressor gene were detected. Wild-type RB protein and cyclin A were expressed in both cells. Our data suggest that these 2 cell lines may be useful in identifying the oncogenetic pattern of RTK.

Antineoplastic Agents↗
PubMed1996

The novel regulatory mechanism of Fas system-mediated apoptosis in mesangial cells: implication to mesangial proliferative glomerulonephritis.

Fas Ag is a cell surface molecule that transduces the signal for apoptosis. Since mesangial cells (MC) play important roles in regulating glomerulonephritis, we investigated regulatory mechanisms of Fas system in MC. Fas Ag was expressed on MC from normal mice. This Fas Ag expression was down-regulated by inducing proliferation with platelet-derived growth factor or 18% fetal bovine serum, but was reversed when cycloheximide was added to the culture. Anti-Fas Ab alone did not induce apoptosis in MC, but MC became susceptible to apoptosis induced by anti-Fas Ab is actinomycin D or cycloheximide was added. Noteworthy findings are that mRNA of Fas ligand was expressed in MC. Taken together, MC appears to control the proliferation by regulating Fas system-mediated apoptosis, at least in part, through an autoregulatory mechanism with Fas Ag Fas ligand expressed on their own MC.

Animals↗
PubMed1996

Rhabdoid tumor of the kidney: a report of two cases with respective tumor markers and a specific chromosomal abnormality, del(11p13).

Malignant rhabdoid tumor is a rare, aggressive, invariably lethal tumor that is resistant to multimodal treatment. In this report, two patients with malignant rhabdoid tumor of the kidney (RTK) are described. The first patient is the first case of RKT with hyperreninemia, and the second case is also the first case with a specific chromosomal abnormality, del 11p13. The first patient presented with hematuria and a mass in the left kidney. Plasma renin, angiotensin, and aldosterone levels were elevated and paralleled the tumor progression. The karyotype of the tumor cells was normal (46,XX). In the second patient, who presented with a mass in the right kidney, the concentration of plasma tissue polypeptide antigen was elevated and paralleled the tumor progression. The karyotype of the tumor cells was 46,XX, del(11)(pter-p13::p12-qter). RTK with a cytogenetic abnormality of del(11p13), which is usually found in aniridia-Wilms' tumor syndrome, has not been known. Both patients died of metastatic disease within 7 months of diagnosis in spite of the multimodal therapy. The clinicopathology of RTK and the differences between Wilms' tumor and RTK raise compelling questions which should be the subject of future studies.

Biomarkers, Tumor↗
PubMed1996

Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutans in the pathogenesis of poststreptococcal glomerulonephritis.

Streptococcus mutans has been shown to share a polysaccharide (PS) antigen with S. pyogenes strains isolated from patients with acute poststreptococcal glomerulonephritis (PSGN), using a monoclonal antibody f-77 reactive with the PS. To investigate the pathogenetic role of the shared PS in PSNG, experimental nephritis was induced in animals. Rats were immunized thrice with heat-killed cells of S. mutans or S. pyogenes, followed by an intravenous injection of live cells of S. pyogenes. Histologic examination showed that both animal groups had comparable degrees of diffuse proliferative nephritis characterized by immune deposits. The shared PS antigen was detected in glomeruli of all nephritic rats by immunofluorescence using monoclonal antibody f-77. Furthermore, all nephritic rats had an elevated antibody titer to the shared PS antigen. These results suggest that prior sensitization (infections such as dental caries) to S. mutans modulates immune responses to subsequent S. pyogenes infections and induces immune-complex disease (PSGN) through the shared PS antigen.

Acute Disease↗
PubMed1996

Detection of hepatitis C virus core protein in the glomeruli of patients with membranous glomerulonephritis.

Two Japanese patients suffered from membranous glomerulonephritis associated with hepatitis C virus (HCV) infection. Renal histologic changes were characterized by granular deposits of IgG and C3 along the capillary wall and numerous subepithelial deposits in glomeruli. Hypocomplementemia was present in one patient, but both cryoglobulins and rheumatoid factors were absent. HCV RNA was detected in both their sera by RT-PCR, both free and in the form of circulating immune complexes. The HCV core protein was found in the glomeruli from both patients by indirect immunofluorescence. These results suggest that in some patients chronic HCV infection causes membranous glomerulonephritis through immune complex deposition involving HCV proteins.

Aged↗
PubMed1995

Acute interstitial nephritis and uveitis with bone marrow granulomas and anti-neutrophil cytoplasmic antibodies.

Acute interstitial nephritis (AIN) and uveitis of unknown etiology developed in a 15-year-old girl. Symptoms and urinary abnormalities improved spontaneously but moderate renal dysfunction and anterior uveitis persisted. A repeat biopsy performed 2 years later showed focal tubulointerstitial changes, while bone marrow examination revealed granulomas. Simultaneously, antineutrophil cytoplasmic antibodies (ANCA) were detected, and decreases in T cell population and lymphocyte function were found. These immunological abnormalities normalized in parallel with clinical improvement with corticosteroid therapy, strongly suggesting that in some patients autoimmune disorders contribute to the pathogenesis of the disease.

Acute Disease↗
PubMed1995

Streptokinase gene variable region classification in streptococci: lack of correlation with post-streptococcal glomerulonephritis.

To investigate a possible causal role of streptokinase (SKase) in acute post-streptococcal glomerulonephritis (APSGN), the major variable region of SKase genes of Streptococcus pyogenes strains isolated from patients with and without APSGN were analyzed using the polymerase chain reaction, restriction enzyme analysis and the direct sequencing of SKase genes. In the APSGN-associated strains, six of nine revealed mutant classes corresponding to the nephritogenic classes I and II proposed by Johnston et al. [1992], the remaining three belonged to non-nephritogenic classes. In twenty strains not associated with APSGN, seventeen belonged to classes I and II, while three were from other classes. The major variable region of the SKase gene shows no apparent relation with induction of APSGN in humans, suggesting that unique classes of streptococcal SKase do not play a role in the pathogenesis of APSGN.

Adolescent↗