Ribozyme Targeting of Receptor for Advanced Glycation End Products in Mouse Mesangial Cells

Accumulation of extracellular matrix is a characteristic of diabetic nephropathy, and advanced glycation end products (AGEs) are considered to play an important role in the mechanism. To investigate the involvement of the receptor for AGE (RAGE) in upregulation of type IV collagen by AGEs, we applie...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-04, Vol.245 (2), p.583-588
Main Authors: Tsuji, Hiroko, Iehara, Noriyuki, Masegi, Tsukio, Imura, Minori, Ohkawa, Jun, Arai, Hidenori, Ishii, Kenji, Kita, Toru, Doi, Toshio
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Line
Cloning, Molecular
Collagen - metabolism
Diabetic Nephropathies - etiology
Gene Expression Regulation - genetics
Glomerular Mesangium - metabolism
Glycation End Products, Advanced - pharmacology
Immunohistochemistry
Mice
Molecular Sequence Data
Receptor for Advanced Glycation End Products
Receptors, Immunologic - genetics
Receptors, Immunologic - metabolism
RNA, Catalytic - metabolism
RNA, Catalytic - therapeutic use
RNA, Messenger - metabolism
Serum Albumin, Bovine - pharmacology
Substrate Specificity
Transfection - genetics
Up-Regulation - physiology
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Summary:Accumulation of extracellular matrix is a characteristic of diabetic nephropathy, and advanced glycation end products (AGEs) are considered to play an important role in the mechanism. To investigate the involvement of the receptor for AGE (RAGE) in upregulation of type IV collagen by AGEs, we applied the hammerhead ribozyme for targeting RAGE. We established a stable mouse mesangial cell line that produces the RAGE-specific ribozyme (Rz-RAGE). Both the RAGE mRNA and protein were decreased in the cell line. The amount of type IV collagen mRNA increased by AGEs’ treatment in control cells. In contrast, the increase of type IV collagen induced by AGEs was not observed in the Rz-RAGE-producing cells. We conclude that the induction of type IV collagen by AGEs is mediated by RAGE and this mechanism could be involved in diabetic nephropathy. This study also suggested the experimental/therapeutic potential of hammerhead ribozymes.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.8489