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  • 1
    Electronic Resource
    Electronic Resource
    IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles (2002)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 7 (2002), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [α-33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.2002.tb00519.x
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  • 2
    Electronic Resource
    Electronic Resource
    Activation of mRNA expression of collagen, collagenase and its inhibitor on renal biopsy specimens in patients with IgA nephropathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 3 (1997), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: In situ hybridization of mRNA for collagen IV, collagen VI, stromelysin (MMP-3) and TIMP1 was examined in renal biopsy specimens from patients with IgA nephropathy (IgAN) or diabetic nephropathy with various degrees of tissue damage. The majority of cells in the glomeruli expressed these mRNA almost simultaneously, but a few cells demonstrated positive expression for only one of these probes. There was a parallel relationship between the degree of tissue damage and that of mRNA expressions of these probes in patients with IgAN, while patients with diabetic nephropathy showed a reverse relationship between these two parameters. It is concluded that patients with mesangial proliferative glomerulonephritis expressed mRNA for collagen collagenase and its inhibitor in the glomeruli in parallel with the progress of tissue damage. In contrast, glomerular samples from patients with diabetic nephropathy showed that there was an inverse relationship between tissue damage and expression of mRNA. It is concluded that expression of collagen, collagenase and its inhibitor parallels the progression of glomerular changes in IgAN, but such parallel expression was not observed in patients with diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1997.tb00196.x
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  • 3
    Electronic Resource
    Electronic Resource
    Intrarenal synthesis of IL-6 in IgA nephropathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 3 (1997), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Recent in vitro studies have shown the synthesis of interleukin-6 (IL-6) in glomerular mesangial and epithelial cells, and suggested the involvement of IL-6 in mesangial proliferative glomerulonephritis. However, the expression site of IL-6 mRNA in renal tissue of IgA nephropathy (IgAN), the most common chronic mesangial proliferative glomerulonephritis, remains obscure. to localize IL-6 mRNA in renal biopsy specimens of IgAN, we used nonradioactive in situ hybridization (ISH) developed in our laboratory, sensitive in detecting individual cells positive for a specific mRNA. In some sections, periodic acid-Schiff staining was performed after ISH in order to identify the topographical relation between IL-6 mRNA positive cells and glomerular basement membrane and mesangial area. In situ hybridization for IL-6 mRNA and immunohistochemistry for CD3 and CD68, markers for lymphocytes and monocytes, respectively, were also performed on serial sections to examine the contribution of infiltrated mononuclear cells to cells positive for IL-6 mRNA in glomeruli. Glomerular resident cells, including glomerular mesangial and epithelial cells and cells of Bowman's capsule, as well as tubular epithelial cells and infiltrated mononuclear cells expressed IL-6 mRNA. We also compared the localization of IL-6 mRNA and protein and showed different distribution between the gene product and protein. the expression of IL-6 mRNA correlated with the degree of mesangial cell proliferation and tubulointerstitial changes. Our results indicate that IL-6 is synthesized in renal tissues of IgAN and suggest that the increased IL-6 expression may be important in the pathogenesis of IgAN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1997.tb00265.x
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  • 4
    Electronic Resource
    Electronic Resource
    Immunohistochemical staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin dependent diabetes mellitus using monoclonal antibody to advanced glycation end products (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 1 (1995), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Immunohistochemical staining of glomeruli in patients with diabetic nephropathy (DN) in non-insulin dependent diabetes mellitus (NIDDM) using the monoclonal anti-advanced glycation end products (AGE) antibody is described. In order to detect the localization of AGE in human renal tissues, we performed immunohistochemical staining using the monoclonal anti-AGE antibody in the glomeruli of 11 patients with DN and 11 age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls.Emergence of AGE in the mesangial area was more marked in the glomeruli of patients with severe mesangial expansion than in those with mild expansion. AGE in the extraglomerular arteriolar walls was also observed. In contrast, there was no positive staining using the same antibody in renal tissue obtained from DPGN.These data support the concept that deposition and/or formation of AGE in the mesangial area might be associated with the progression of diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1995.tb00028.x
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  • 5
    Electronic Resource
    Electronic Resource
    Profiling the IgA nephropathy renal transcriptome: analysis by complementary DNA array hybridization (2002)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 7 (2002), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: A comprehensive profile of genes expressed at the mRNA level (transcriptome) in human renal tissue is important for elucidating the pathogenesis and treatment of IgA nephropathy (IgAN). the recent development of complementary DNA (cDNA) array hybridization allows the parallel monitoring of thousands of genes expressed in renal tissue. High-density cDNA containing 18326 paired unique human cDNA gene probes were used to quantitatively analyse the expression of genes in renal biopsies of IgAN and controls. Computational analysis was used to cluster genes according to similarity in pattern of gene expression. Through relational database analysis, we determined 1901 genes that were commonly expressed in four selected IgAN renal biopsies and four controls. Further analysis of the expressed genes by self-organizing maps and hierarchical clustering revealed a genomic profile unique to severely affected IgAN patients. These findings represent a comprehensive preliminary molecular index of genes transcribed in IgAN. More importantly, this molecular approach may accelerate the discovery of pathogenic mechanisms underlying the most common form of glomerulonephritis worldwide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.2002.tb00524.x
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  • 6
    Electronic Resource
    Electronic Resource
    Glomerular expression of connective tissue growth factor mRNA in various renal diseases (2003)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 8 (2003), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY:  Connective tissue growth factor (CTGF) is a cysteine-rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA-N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA-N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high-resolution in situ hybridization with digoxigenin-labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF-positive cytoplasm, in at least 10 randomly selected cross-sections of non-sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowman's capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA-N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA-positive cells between DN and IgA-N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA-N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end-stage renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1797.2003.00142.x
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  • 7
    Electronic Resource
    Electronic Resource
    Altered immunity in circulation of patients with IgA nephropathy (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 3 (1997), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Several abnormalities of the immune system are assumed to be involved in the development of IgA nephropathy (IgAN). the roles of cytokines and other soluble factors, which may interact mutually in peripheral circulation, have been studied by many investigators who believed that analysis of the source and function of such factors might provide a significant clue in order to disclose the mechanisms of development of IgAN. Changes in B cell immunity such as enhanced production of IgA or IgE have been reported in IgAN. B cells in IgAN also showed enhanced expression of CD23 (Fc&RII) on their surface. Th2 cell derived pleiotropic cytokine, interleukin (IL)-4 is known as potent inducer for CD23, IgE and IgA. In IgAN, synthesis of IL-4 is enhanced both in vivo and in vitro. Th1 derived cytokine, interferon (IFN)-γ is a antagonist to Th2 derived cytokines. Although, in vitro synthesis of the cytokine is unexpectedly increased in IgAN, its suppressive effects against IL-4 are, at least partially, impeded in IgAN. Under this condition, relatively enhanced Th2 like cell activity may help to keep B cell activation in IgAN. Increased numbers of human leukocyte antigen (HLA)-DR bearing natural killer (NK) cells are observed in IgAN. These HLA positive NK cells simultaneously express high IFN-γ genes. These NK cells are possibly the source of increased IFN-γ in IgAN and play a compensatory roles for suppressed Th1-like cells. Interferon-γ production by NK cells in IgAN is probably regulated by IL-12. Although the source of IL-12 in circulation has not been determined, characteristically activated B cells in IgAN, other than macrophages, may have some relation to this IL-12 - NK- IFN-γ cascade. the HLA-bearing rate of NK cells in IgAN showed a positive relation to rapidity of progression of renal dysfunction in a long-term follow-up study. These findings suggested that IgA specific changes in peripheral cell interaction involving Th2-like cells, B cells, macrophages and NK cells may be able to induce local inflammatory events in the kidneys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1997.tb00283.x
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  • 8
    Electronic Resource
    Electronic Resource
    IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles (2002)
    Oxford, UK : Blackwell Science Pty
    Nephrology 7 (2002), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. The expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [α-33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Approximately 8212 ± 530 different gene transcripts were detected per target. Close to 5% (386 ± 90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1797.7.s3.5.x
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    Paper (German National Licenses)
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  • 9
    Electronic Resource
    Electronic Resource
    Detection of monocyte chemoattractant protein-1 (MCP-1) and its receptors in mesangial proliferative glomerulonephritis (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Nephrology 2 (1996), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: There are many reports suggesting that tissue damage in chronic glomerulonephritis (CGN) might be related to macrophages, and that a variety of chemotactic factors (intercrine or chemokine) activate macrophages. Monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, has been suggested to be both an important monocyte chemotaxin and activator in renal inflammation. Here, we studied the expression of MCP-1 and its receptors, both common (CKR-1), as well as specific (MCP-la and MCP-1b) in human renal tissues at mRNA levels by reverse transcriptase polymerase chain reaction (RT-PCR) assay. Total RNA was extracted from renal tissues that were obtained from 40 patients. Separation of the glomeruli was performed in 17 patients. There was stronger MCP-1 mRNA expression in the whole renal tissue samples than in the isolated glomeruli. the expression of MCP-1 receptor was also greater in the whole tissue than in the glomeruli. Moreover, the expression of MCP-1 mRNA was correlated with the levels of serum creatinine, creatinine clearance (Ccr) and interstitial tissue damage. Finally, our study shows the infiltration of macrophages was strongly demonstrated in the interstitium by monoclonal antibody (CD68) using the ABC method, and it has a correlation with the frequency of MCP-1 positive group. We concluded that MCP-1 might be connected with the pathogenesis of mesangial proliferative glomerulonephritis (mesPGN) and that interstitial events might be related to the progression of mesPGN.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.1996.tb00071.x
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  • 10
    Electronic Resource
    Electronic Resource
    Significance of alpha-smooth muscle actin expression in IgA nephropathy: Revisited (2004)
    Melbourne, Australia : Blackwell Science Pty
    Nephrology 9 (2004), S. 0 
    Details
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1797.2004.00280.x
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