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Inhibiting albumin glycation in vivo ameliorates glomerular overexpression of TGF-beta1.

Authors
 Margo P. Cohen  ;  Fuad N. Ziyadeh  ;  Soon Won Hong  ;  Clyde W. Shearman  ;  Elizabeth Hud  ;  Gregory T. Lautenslager  ;  M. Carmeniglesias-de La Cruz  ;  Sheldon Chen 
Citation
 KIDNEY INTERNATIONAL, Vol.61(6) : 2025-2032, 2002 
Journal Title
KIDNEY INTERNATIONAL
ISSN
 0085-2538 
Issue Date
2002
MeSH
Albuminuria/etiology ; Aniline Compounds/pharmacology* ; Animals ; Diabetes Mellitus/genetics* ; Diabetes Mellitus/metabolism* ; Diabetes Mellitus/pathology ; Diabetes Mellitus/urine ; Diclofenac/analogs & derivatives* ; Diclofenac/pharmacology ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/metabolism* ; Kidney Glomerulus/pathology ; Male ; Mice ; Mice, Mutant Strains/genetics ; Phenylacetates/pharmacology* ; Serum Albumin/antagonists & inhibitors* ; Transforming Growth Factor beta/metabolism* ; Transforming Growth Factor beta1
Keywords
diabetic nephropathy ; transforming growth factor-β1 ; glycated albumin ; db/db mouse ; hyperglycemia
Abstract
Inhibiting albumin glycation in vivo ameliorates glomerular overexpression of TGF-beta1.
[Background] Glycated albumin has been causally linked to the pathobiology of diabetic renal disease through its ability to stimulate the expression of transforming growth factor-beta1 (TGF-beta1), activate protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), and promote production of extracellular matrix proteins in cultured glomerular cells. Whether glycated albumin modulates glomerular TGF-beta1 expression in vivo is not known. To address this issue, we assessed glomerular TGF-beta1 expression and pathology in response to reducing the burden of glycated albumin in vivo.
[Methods] We measured serum glycated albumin, urine protein, glomerular TGF-beta1 expression and morphometry, and collagen IV and fibronectin mRNA in db/m and db/db controls and in db/db mice treated for eight weeks with a synthetic compound that inhibits the condensation of glucose with albumin.
[Results] In situ hybridization studies showed markedly increased glomerular TGF-beta1 mRNA in control db/db mice, which was significantly reduced in db/db mice treated for eight weeks with test compound. The treatment protocol, which normalized serum glycated albumin, concomitantly reduced the elevated protein excretion and the renal overexpression of mRNAs encoding fibronectin and collagen IV, and significantly decreased the mesangial matrix expansion, observed in db/db control animals.
[Conclusions] These findings, to our knowledge, provide the first evidence that glomerular overexpression of TGF-beta1 in diabetes derives at least in part from elevated glycated albumin concentrations, and can be partially suppressed by inhibiting the formation of this glycated protein. The results further suggest that glycated albumin has an important nephropathogenic role in diabetes that is operative, and can be therapeutically addressed, independent of glycemic status.
Files in This Item:
T200202787.pdf Download
DOI
10.1046/j.1523-1755.2002.00352.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143497
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