Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy

The mechanism of structural changes of the kidney in human diabetic nephrop athy (DN) and IgA nephropathy (IgAN) is not yet completely known, but exces sive deposition of extracellular matrix (ECM), including various collagens, may be crucial to this process. Heat shock protein (HSP) 47 has been ident ified as collagen-binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assem bly. 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 HSP4 7, type III collagen and type IV collagen were used to assess the relative expression of their proteins in paraffin-embedded renal sections by immunoh istochemistry. Increased deposition of collagens was closely related to the sclerotic activity of the disease process in DN and IgAN; increased deposi tion of collagens was often present in relation to a strong expression of H SP47, a stress protein known to regulate collagen synthesis/assembly. By do uble immunostaining, we found colocalization of collagens and their molecul ar 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 rol e in the excessive assembly of collagens resulting in glomerulosclerosis an d interstitial fibrosis found in DN and IgAN patients.