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Topics {✒️}

human gbm-hspg-core protein glomerular heparan-35so4 proteoglycan human glomerular diseases extracellular matrix components hspg-core protein staining streptozotocin-induced diabetic mice glomerular basement membrane streptozotocin-induced diabetic rats heparan sulphate proteoglycan insulin-dependent diabetic patients hs side chain anti-collagen type iv extracellular matrix diabetic renal disease basement membrane constituents privacy choices/manage cookies hspg-core protein martinus nijhoff publishing decreased hs staining normal control subjects human diabetic nephropathy single glomerular proteomics global glomerular sclerosis glomerular arteriolar hyalinosis related subjects van den born van den born  insulin dependent diabetes light chain isotypes predicting diabetic nephropathy charge-dependent permeability insulin-dependent patients basement membrane mesangial matrix heparan sulphate decreased gbm staining diabetic glomerulosclerosis glomerular filtration rate glomerular proteoglycan conditions privacy policy increased mesangial staining renal function test collagen type iii compare hspg expression european economic area structural-functional relationships accepting optional cookies scope submit manuscript monoclonal igg deposits 35s-glycopeptide metabolism

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WebPage:
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         headline:Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane
         description:Diabetic nephropathy is characterized by albuminuria which proceeds to overt proteinuria. The highly negatively stained HS side chain of heparan sulphate proteoglycan (HSPG) is a major determinant of the charge-dependent permeability of the GBM. We set out to study the presence of HS and HSPG in the GBM of patients with diabetic nephropathy using newly developed monoclonal antibodies, and to compare HSPG expression to the expression of other previously investigated glomerular extracellular matrix compounds. Immunohistochemically, glomerular extracellular matrix components were analysed in 14 renal biopsies of patients with diabetic nephropathy and compared with those of normal control subjects. Monoclonal antibodies used were: JM403 against the HS side chain of GBM HSPG and JM72 against the HSPG-core protein. Also, a polyclonal antiserum (B31) against human GBM-HSPG-core protein was used. Additionally, antibodies were used against collagen types I, III, IV and against α1(IV)NC, α3(IV)NC and fibronectin. Staining was scored for intensity and for staining pattern by four independent observers who had no previous knowledge of the sample origin. No glomerular staining was seen for collagen type I. Collagen type III was present in some diabetic nodules. Anti-collagen type IV showed a decreased GBM staining in patients with diabetic nephropathy (p = 0.04). With anti-α1(IV)NC no changes in GBM staining intensity were observed; with anti-α3(IV)NC brilliant GBM staining was seen in both groups. Increased mesangial staining (p = 0.003) was seen with anti-collagen type IV in biopsies with nodular lesions. No differences were observed for fibronectin although it was abundantly present in the mesangial area of biopsies from patients with diabetic nephropathy. In biopsies with mesangial expansion and in biopsies with diabetic nodules, we observed a decreased GBM (p = 0.001) HS side chain staining (JM403) without changes in HSPG-core protein staining (JM72,B31). The HS staining pattern regularly changed from a linear to a more granular and irregular pattern. In patients with a creatinine clearance of more than 15 ml/min, the intensity of GBM HS staining showed an inverse correlation with the rate of proteinuria (r = -0.85, p = 0.004), suggesting a functional relationship. The decreased HS staining in the GBM may reflect the potentially disrupted charge barrier in diabetic nephropathy.
         datePublished:
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            Diabetic nephropathy
            heparan sulphate
            heparan sulphate proteoglycan
            glomerular basement membrane
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            Internal Medicine
            Metabolic Diseases
            Human Physiology
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      headline:Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane
      description:Diabetic nephropathy is characterized by albuminuria which proceeds to overt proteinuria. The highly negatively stained HS side chain of heparan sulphate proteoglycan (HSPG) is a major determinant of the charge-dependent permeability of the GBM. We set out to study the presence of HS and HSPG in the GBM of patients with diabetic nephropathy using newly developed monoclonal antibodies, and to compare HSPG expression to the expression of other previously investigated glomerular extracellular matrix compounds. Immunohistochemically, glomerular extracellular matrix components were analysed in 14 renal biopsies of patients with diabetic nephropathy and compared with those of normal control subjects. Monoclonal antibodies used were: JM403 against the HS side chain of GBM HSPG and JM72 against the HSPG-core protein. Also, a polyclonal antiserum (B31) against human GBM-HSPG-core protein was used. Additionally, antibodies were used against collagen types I, III, IV and against α1(IV)NC, α3(IV)NC and fibronectin. Staining was scored for intensity and for staining pattern by four independent observers who had no previous knowledge of the sample origin. No glomerular staining was seen for collagen type I. Collagen type III was present in some diabetic nodules. Anti-collagen type IV showed a decreased GBM staining in patients with diabetic nephropathy (p = 0.04). With anti-α1(IV)NC no changes in GBM staining intensity were observed; with anti-α3(IV)NC brilliant GBM staining was seen in both groups. Increased mesangial staining (p = 0.003) was seen with anti-collagen type IV in biopsies with nodular lesions. No differences were observed for fibronectin although it was abundantly present in the mesangial area of biopsies from patients with diabetic nephropathy. In biopsies with mesangial expansion and in biopsies with diabetic nodules, we observed a decreased GBM (p = 0.001) HS side chain staining (JM403) without changes in HSPG-core protein staining (JM72,B31). The HS staining pattern regularly changed from a linear to a more granular and irregular pattern. In patients with a creatinine clearance of more than 15 ml/min, the intensity of GBM HS staining showed an inverse correlation with the rate of proteinuria (r = -0.85, p = 0.004), suggesting a functional relationship. The decreased HS staining in the GBM may reflect the potentially disrupted charge barrier in diabetic nephropathy.
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      dateModified:
      pageStart:313
      pageEnd:320
      sameAs:https://doi.org/10.1007/BF00398060
      keywords:
         Diabetic nephropathy
         heparan sulphate
         heparan sulphate proteoglycan
         glomerular basement membrane
         extracellular matrix
         Internal Medicine
         Metabolic Diseases
         Human Physiology
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      name:Department of Nephrology, University Hospital Nijmegen, The Netherlands
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      name:Department of Pathology, University of Groningen, The Netherlands
      name:Department of Pathology, University of Amsterdam, The Netherlands
      name:Department of Nephrology, University Hospital Nijmegen, The Netherlands
      name:Department of Autoimmune Serology, Statens Seruminstitut, Copenhagen, Denmark
      name:Department of Nephrology, University Hospital Leiden, The Netherlands
      name:Department of Medical Statistics, University of Leiden, The Netherlands
      name:Department of Biochemistry, University of Nijmegen, The Netherlands
      name:Department of Pathology, University Hospital Leiden, The Netherlands
      name:Department of Pathology, University Hospital Leiden, The Netherlands

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