Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-04

AUTHORS

K. Tsuchida, Z. Makita, S. Yamagishi, T. Atsumi, H. Miyoshi, S. Obara, M. Ishida, S. Ishikawa, K. Yasumura, T. Koike

ABSTRACT

Aims/hypothesis. Advanced glycation end products (AGEs) participate in the pathogenesis of diabetic nephropathy. We reported earlier that OPB-9195, a synthetic thiazolidine derivative and novel inhibitor of advanced glycation, prevented progression of diabetic glomerulosclerosis by lowering serum concentrations of advanced glycation end products and reducing their deposition in the glomeruli. Here, we examined their contribution and that of growth factors, such as transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF), to the progression of diabetic nephropathy. We also investigated the expression of type IV collagen in the kidneys of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model, after treatment with OPB-9195. Methods. Using northern blots and immunohistochemical techniques, we determined the renal expression of TGF-β and type IV collagen mRNAs and proteins in OLETF rats. We also examined OPB-9195's effects on renal expression of VEGF mRNA and protein. Results. Concomitant increases in TGF-β and type IV collagen expression were observed at each point in time in OLETF rats not given OPB-9195. In contrast, OPB-9195 treatment greatly suppressed the renal expression of TGF-β, VEGF and type IV collagen mRNAs and proteins to that seen in non-diabetic rats. Conclusion/interpretation. Since OPB-9195, an AGE-inhibitor, prevented the progression of diabetic nephropathy by blocking type IV collagen production and suppressing overproduction of two growth factors, TGF-β and VEGF, in diabetic rats, this compound warrants further investigation. [Diabetologia (1999) 42: 579–588] More... »

PAGES

579-588

Journal

TITLE

Diabetologia

ISSUE

5

VOLUME

42

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s001250051198

DOI

http://dx.doi.org/10.1007/s001250051198

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042150322

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10333051


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