Tags

Type your tag names separated by a space and hit enter

High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1.
Am J Pathol. 2007 Sep; 171(3):744-54.AJ

Abstract

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.

Authors+Show Affiliations

Dept. of Medicine, University of Sydney, Sydney, New South Wales, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17675577

Citation

Qi, Weier, et al. "High Glucose-induced Thioredoxin-interacting Protein in Renal Proximal Tubule Cells Is Independent of Transforming Growth Factor-beta1." The American Journal of Pathology, vol. 171, no. 3, 2007, pp. 744-54.
Qi W, Chen X, Gilbert RE, et al. High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. Am J Pathol. 2007;171(3):744-54.
Qi, W., Chen, X., Gilbert, R. E., Zhang, Y., Waltham, M., Schache, M., Kelly, D. J., & Pollock, C. A. (2007). High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. The American Journal of Pathology, 171(3), 744-54.
Qi W, et al. High Glucose-induced Thioredoxin-interacting Protein in Renal Proximal Tubule Cells Is Independent of Transforming Growth Factor-beta1. Am J Pathol. 2007;171(3):744-54. PubMed PMID: 17675577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High glucose-induced thioredoxin-interacting protein in renal proximal tubule cells is independent of transforming growth factor-beta1. AU - Qi,Weier, AU - Chen,Xinming, AU - Gilbert,Richard E, AU - Zhang,Yuan, AU - Waltham,Mark, AU - Schache,Maria, AU - Kelly,Darren J, AU - Pollock,Carol A, Y1 - 2007/08/03/ PY - 2007/8/7/pubmed PY - 2007/12/7/medline PY - 2007/8/7/entrez SP - 744 EP - 54 JF - The American journal of pathology JO - Am J Pathol VL - 171 IS - 3 N2 - 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. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/17675577/High_glucose_induced_thioredoxin_interacting_protein_in_renal_proximal_tubule_cells_is_independent_of_transforming_growth_factor_beta1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62007-X DB - PRIME DP - Unbound Medicine ER -