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      Coexpression of Collagens and Collagen-Binding Heat Shock Protein 47 in Human Diabetic Nephropathy and IgA Nephropathy


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          The mechanism of structural changes of the kidney in human diabetic nephropathy (DN) and IgA nephropathy (IgAN) is not yet completely known, but excessive deposition of extracellular matrix (ECM), including various collagens, may be crucial to this process. Heat shock protein (HSP) 47 has been identified as collagen-binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assembly. To determine whether increased deposition of collagens in human DN and IgAN is related to HSP47, we investigated the expression of HSP47 in renal biopsy and autopsy sections obtained from 22 DN and 45 IgAN patients. Five renal biopsy specimens, diagnosed as minor glomerular abnormalities, were simultaneously studied as controls. Monoclonal antibodies specific for HSP47, type III collagen and type IV collagen were used to assess the relative expression of their proteins in paraffin-embedded renal sections by immunohistochemistry. Increased deposition of collagens was closely related to the sclerotic activity of the disease process in DN and IgAN; increased deposition of collagens was often present in relation to a strong expression of HSP47, a stress protein known to regulate collagen synthesis/assembly. By double immunostaining, we found colocalization of collagens and their molecular chaperone HSP47 in the sclerotic glomeruli and tubulointerstitium in DN and IgAN. Our results strongly support a pathologic role for HSP47 in both these diseases and that increased levels of HSP47 may play an important role in the excessive assembly of collagens resulting in glomerulosclerosis and interstitial fibrosis found in DN and IgAN patients.

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          Author and article information

          S. Karger AG
          December 1998
          07 December 1998
          : 80
          : 4
          : 434-443
          a Second Department of Pathology, b Department of Biochemistry, Institute of Tropical Medicine, and c Second Department of Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
          45217 Nephron 1998;80:434–443
          © 1998 S. Karger AG, Basel

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          Page count
          Figures: 6, Tables: 2, References: 26, Pages: 10
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/45217
          Self URI (text/html): https://www.karger.com/Article/FullText/45217
          Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
          Original Paper

          Cardiovascular Medicine,Nephrology
          Diabetic nephropathy,IgA nephropathy,Collagen,Heat shock protein 47


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