Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress collagen accumulation in experimental glomerulonephritis.
Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the biosynthesis and secretion of procollagen molecules. The expression of HSP47 has been reported to increase in parallel with the expression of collagens during the progression of various fibrosis models. However, it remains unclear whether an inhibition of HSP47 overexpression would suppress collagen accumulation and thus reduce the progression of fibrotic diseases. In this study, we attempted to attenuate glomerular collagen accumulation by inhibiting the overexpression of HSP47 with antisense oligodeoxynucleotides in an experimental glomerulonephritis model induced by anti-Thy-1 antibodies. The administration of antisense oligodeoxynucleotides against HSP47 at the induction of the glomerular disease markedly suppressed the increased production of collagens and attenuated the histologic manifestations of the disease. These results provide direct evidence of a pivotal role for HSP47 in the pathogenesis of glomerulonephritis.
Department of Clinical Bio-Regulatory Science, Faculty of Medicine, Kyoto University, Japan.
M
M
Sunamoto
K
K
Kuze
H
H
Tsuji
N
N
Ohishi
K
K
Yagi
K
K
Nagata
T
T
Kita
T
T
Doi
D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; C494662:Serpinh1 protein, rat; D013873:Thionucleotides; D003094:Collagen