ANTISENSE OLIGONUCLEOTIDES AGAINST COLLAGEN-BINDING STRESS PROTEIN HSP47 SUPPRESS COLLAGEN ACCUMULATION IN EXPERIMENTAL GLOMERULONEPHRITIS

Heat shock protein 47 (HSP47) is a collagen-specific molecular chapero ne that has been shown to play a major role during the biosynthesis an d secretion of procollagen molecules. The expression of HSP47 has been reported to increase in parallel with the expression of collagens dur ing the progression of various fibrosis models. However, it remains un clear whether an inhibition of HSP47 overexpression would suppress col lagen accumulation and thus reduce the progression of fibrotic disease s. In this study, we attempted to attenuate glomerular collagen accumu lation by inhibiting the overexpression of HSP47 with antisense oligod eoxynucleotides in an experimental glomerulonephritis model induced by anti-Thy-1 antibodies. The administration of antisense oligodeoxynucl eotides against HSP47 at the induction of the glomerular disease marke dly suppressed the increased production of collagens and attenuated th e histologic manifestations of the disease. These results provide dire ct evidence of a pivotal role for HSP47 in the pathogenesis of glomeru lonephritis.