1995
DOI: 10.2337/diab.44.8.895
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Effect of a Specific Endothelin Receptor A Antagonist on mRNA Levels for Extracellular Matrix Components and Growth Factors in Diabetic Glomeruli

Abstract: We have previously reported that the mRNA levels of extracellular matrix (ECM) components including alpha 1(I), alpha 1(III), and alpha 1(IV) collagen chains, laminin B1 and B2 chains, and growth factors including tumor necrosis factor (TNF)-alpha, platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF)-beta, and basic fibroblast growth factor (FGF) all increase with age in diabetic glomeruli. The present study was designed to assess whether glomerular expression of these mRNAs in rat d… Show more

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Cited by 105 publications
(69 citation statements)
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“…Treatment with an ETA receptor antagonist as well as with a combined ETA/ETB receptor antagonist completely abolished this increased glomerular matrix synthesis. Our data are in agreement with a report showing also a beneficial effect of an ETA antagonist on glomerular mRNA coding for growth factors and matrix proteins in diabetic rats [16]. However, it is even more important to analyze the matrix synthesis on the protein level in order to answer the question whether or not ET contributes to increased matrix synthesis in early diabetic nephropathy, since it is well known that matrix synthesis is often regulated by both (i) modulation of the mRNA coding for matrix proteins and (ii) the synthesis of proteins/factors that are involved in matrix degradation (e.g., TIMP-1).…”
Section: Discussionsupporting
confidence: 83%
See 1 more Smart Citation
“…Treatment with an ETA receptor antagonist as well as with a combined ETA/ETB receptor antagonist completely abolished this increased glomerular matrix synthesis. Our data are in agreement with a report showing also a beneficial effect of an ETA antagonist on glomerular mRNA coding for growth factors and matrix proteins in diabetic rats [16]. However, it is even more important to analyze the matrix synthesis on the protein level in order to answer the question whether or not ET contributes to increased matrix synthesis in early diabetic nephropathy, since it is well known that matrix synthesis is often regulated by both (i) modulation of the mRNA coding for matrix proteins and (ii) the synthesis of proteins/factors that are involved in matrix degradation (e.g., TIMP-1).…”
Section: Discussionsupporting
confidence: 83%
“…(a) It seems unlikely that the antifibrotic effect is related to a blood pressue reduction, since all published studies analyzing the long-term effect of ET receptor antagonists in this rat model of diabetes (STZ-induced diabetes) do not report any significant blood-pressure-lowering effect of ET receptor antagonists at the end of the study [15, 16, 17]. However, we could not completely exclude a blood pressure effect on matrix synthesis in the present study, since blood pressure was not measured.…”
Section: Discussionmentioning
confidence: 99%
“…Proteinuria is thought to be nephrotoxic and a very good predictor of the rate of progression of chronic renal failure [45, 46]. Since ET A receptor antagonists can reduce proteinuria [44], the upregulation of ET A receptors may increase proteinuria, leading to further renal damage.…”
Section: Discussionmentioning
confidence: 99%
“…Since ET-1 can induce the synthesis of TGF-β and PDGF [17], it is not surprising that in diabetic patients there is an increased production of TGF-β [43]. The treatment of diabetic rats with an ET A receptor antagonist can lead to a reduction in the TGF-β expression in glomeruli as well as a decrease in albuminuria and matrix gene expression [44]. Hence, the ET-1-induced expression of TGF-β may be mediated via ET A receptor stimulation.…”
Section: Discussionmentioning
confidence: 99%
“…Effects of endothelin on target cells include increased renal vascular resistance and decreased glomerular filtration, renal blood flow, and vasoconstriction of smooth muscle cells. Endothelin I induces mesangial proliferation and contraction, inducing the mRNA expression of the extracellular matrix in several types of renal diseases [51, 52, 53, 54, 55, 56, 57, 58]. This effect is influenced by cytokines [51].…”
Section: Renal Pathophysiologymentioning
confidence: 99%