High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1.

High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Research Abstract Details 

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High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Abstract Text:

Weier Qi,Xinming Chen,Richard E Gilbert,Yuan Zhang,Mark Waltham,Maria Schache,Darren J Kelly,Carol A Pollock,Weier Qi,Xinming Chen,Richard E Gilbert,Yuan Zhang,Mark Waltham,Maria Schache,Darren J Kelly,Carol A Pollock,

Hyperglycemia is a causative factor in the pathogenesis of diabetic nephropathy. Here, we demonstrate the transcriptional profiles of the human proximal tubule cell line (HK-2 cells) exposed to high glucose using cDNA microarray analysis. Thioredoxin-interacting protein (Txnip) was the gene most significantly increased among 10 strongly up-regulated and 15 down-regulated genes. Txnip, heat shock proteins 70 and 90, chemokine (C-C motif) ligand 20, and matrix metalloproteinase-7 were chosen for verification of gene expression. Real-time reverse transcriptase-polymerase chain reaction confirmed the mRNA expression levels of these five genes, consistent with microarray analysis. The increased protein expression of Txnip, CCL20, and MMP7 were also verified by Western blotting and enzyme-linked immunosorbent assay. Increased expression of Txnip and of nitrotyrosine, as a marker of oxidative stress, were confirmed in vivo in diabetic Ren-2 rats. Subsequent studies focused on the dependence of Txnip expression on up-regulation of transforming growth factor (TGF)-beta1 under high-glucose conditions. Overexpression of Txnip and up-regulation of Txnip promoter activity were observed in cells in which the TGF-beta1 gene was silenced in HK-2 cells using short interfering RNA technology. High glucose further increased both Txnip expression and its promoter activity in TGF-beta1 silenced cells compared with wild-type cells exposed to high glucose, suggesting that high glucose induced Txnip through a TGF-beta1-indepen-dent pathway.

High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Publishing Authors By Initials

W Qi,X Chen,RE Gilbert,Y Zhang,M Waltham,M Schache,DJ Kelly,CA Pollock,W Qi,X Chen,RE Gilbert,Y Zhang,M Waltham,M Schache,DJ Kelly,CA Pollock,

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High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The American journal of pathology

VOLUME: 171

Page Numbers: 744-54

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 3

MONTH: 08

YEAR: 2007

High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Information

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LANGUAGE: eng

NlmUniqueID: 370502

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Grant and Affiliation Information for High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1.

AFFILIATION: Dept. of Medicine, University of Sydney, Sydney, New South Wales, Australia.

Country: United States

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MEDLINETA: Am J Pathol

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