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Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy

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Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy. / Brennan, Eoin P; Morine, Melissa J; Walsh, David W; Roxburgh, Sarah A; Lindenmeyer, Maja T; Brazil, Derek P; Gaora, Peadar Ó; Roche, Helen M; Sadlier, Denise M; Cohen, Clemens D; Godson, Catherine; Martin, Finian; GENIE Consortium.

In: Biochim Biophys Acta, Vol. 1822, No. 4, 04.2012, p. 589-99.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Brennan, EP, Morine, MJ, Walsh, DW, Roxburgh, SA, Lindenmeyer, MT, Brazil, DP, Gaora, PÓ, Roche, HM, Sadlier, DM, Cohen, CD, Godson, C, Martin, F & GENIE Consortium 2012, 'Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy', Biochim Biophys Acta, vol. 1822, no. 4, pp. 589-99. https://doi.org/10.1016/j.bbadis.2012.01.008

APA

Brennan, E. P., Morine, M. J., Walsh, D. W., Roxburgh, S. A., Lindenmeyer, M. T., Brazil, D. P., Gaora, P. Ó., Roche, H. M., Sadlier, D. M., Cohen, C. D., Godson, C., Martin, F., & GENIE Consortium (2012). Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy. Biochim Biophys Acta, 1822(4), 589-99. https://doi.org/10.1016/j.bbadis.2012.01.008

Vancouver

Brennan EP, Morine MJ, Walsh DW, Roxburgh SA, Lindenmeyer MT, Brazil DP et al. Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy. Biochim Biophys Acta. 2012 Apr;1822(4):589-99. https://doi.org/10.1016/j.bbadis.2012.01.008

Bibtex

@article{dc0aad5d1b0a4657a72d1494c01860c7,
title = "Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy",
abstract = "Transforming growth factor-beta (TGF-β1) is implicated in the onset and progression of renal fibrosis and diabetic nephropathy (DN), leading to a loss of epithelial characteristics of tubular cells. The transcriptional profile of renal tubular epithelial cells stimulated with TGF-β1 was assessed using RNA-Seq, with 2027 differentially expressed genes identified. Promoter analysis of transcription factor binding sites in the TGF-β1 responsive gene set predicted activation of multiple transcriptional networks, including NFκB. Comparison of RNA-Seq with microarray data from identical experimental conditions identified low abundance transcripts exclusive to RNA-Seq data. We compared these findings to human disease by analyzing transcriptomic data from renal biopsies of patients with DN versus control groups, identifying a shared subset of 179 regulated genes. ARK5, encoding an AMP-related kinase, and TGFBI - encoding transforming growth factor, beta-induced protein were induced by TGF-β1 and also upregulated in human DN. Suppression of ARK5 attenuated fibrotic responses of renal epithelia to TGF-β1 exposure; and silencing of TGFBI induced expression of the epithelial cell marker - E-cadherin. We identified low abundance transcripts in sequence data and validated expression levels of several transcripts (ANKRD56, ENTPD8) in tubular enriched kidney biopsies of DN patients versus living donors. In conclusion, we have defined a TGF-β1-driven pro-fibrotic signal in renal epithelial cells that is also evident in the DN renal transcriptome.",
keywords = "Blotting, Western, Cell Line, Diabetic Nephropathies, Epithelial Cells, Gene Expression Profiling, Humans, Kidney, Polymerase Chain Reaction, Transforming Growth Factor beta1, Journal Article, Research Support, Non-U.S. Gov't",
author = "Brennan, {Eoin P} and Morine, {Melissa J} and Walsh, {David W} and Roxburgh, {Sarah A} and Lindenmeyer, {Maja T} and Brazil, {Derek P} and Gaora, {Peadar {\'O}} and Roche, {Helen M} and Sadlier, {Denise M} and Cohen, {Clemens D} and Catherine Godson and Finian Martin and {GENIE Consortium}",
note = "Copyright {\^A}{\textcopyright} 2011 Elsevier B.V. All rights reserved.",
year = "2012",
month = apr,
doi = "10.1016/j.bbadis.2012.01.008",
language = "English",
volume = "1822",
pages = "589--99",
journal = "Biochim Biophys Acta",
issn = "0006-3002",
number = "4",

}

RIS

TY - JOUR

T1 - Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy

AU - Brennan, Eoin P

AU - Morine, Melissa J

AU - Walsh, David W

AU - Roxburgh, Sarah A

AU - Lindenmeyer, Maja T

AU - Brazil, Derek P

AU - Gaora, Peadar Ó

AU - Roche, Helen M

AU - Sadlier, Denise M

AU - Cohen, Clemens D

AU - Godson, Catherine

AU - Martin, Finian

AU - GENIE Consortium

N1 - Copyright © 2011 Elsevier B.V. All rights reserved.

PY - 2012/4

Y1 - 2012/4

N2 - Transforming growth factor-beta (TGF-β1) is implicated in the onset and progression of renal fibrosis and diabetic nephropathy (DN), leading to a loss of epithelial characteristics of tubular cells. The transcriptional profile of renal tubular epithelial cells stimulated with TGF-β1 was assessed using RNA-Seq, with 2027 differentially expressed genes identified. Promoter analysis of transcription factor binding sites in the TGF-β1 responsive gene set predicted activation of multiple transcriptional networks, including NFκB. Comparison of RNA-Seq with microarray data from identical experimental conditions identified low abundance transcripts exclusive to RNA-Seq data. We compared these findings to human disease by analyzing transcriptomic data from renal biopsies of patients with DN versus control groups, identifying a shared subset of 179 regulated genes. ARK5, encoding an AMP-related kinase, and TGFBI - encoding transforming growth factor, beta-induced protein were induced by TGF-β1 and also upregulated in human DN. Suppression of ARK5 attenuated fibrotic responses of renal epithelia to TGF-β1 exposure; and silencing of TGFBI induced expression of the epithelial cell marker - E-cadherin. We identified low abundance transcripts in sequence data and validated expression levels of several transcripts (ANKRD56, ENTPD8) in tubular enriched kidney biopsies of DN patients versus living donors. In conclusion, we have defined a TGF-β1-driven pro-fibrotic signal in renal epithelial cells that is also evident in the DN renal transcriptome.

AB - Transforming growth factor-beta (TGF-β1) is implicated in the onset and progression of renal fibrosis and diabetic nephropathy (DN), leading to a loss of epithelial characteristics of tubular cells. The transcriptional profile of renal tubular epithelial cells stimulated with TGF-β1 was assessed using RNA-Seq, with 2027 differentially expressed genes identified. Promoter analysis of transcription factor binding sites in the TGF-β1 responsive gene set predicted activation of multiple transcriptional networks, including NFκB. Comparison of RNA-Seq with microarray data from identical experimental conditions identified low abundance transcripts exclusive to RNA-Seq data. We compared these findings to human disease by analyzing transcriptomic data from renal biopsies of patients with DN versus control groups, identifying a shared subset of 179 regulated genes. ARK5, encoding an AMP-related kinase, and TGFBI - encoding transforming growth factor, beta-induced protein were induced by TGF-β1 and also upregulated in human DN. Suppression of ARK5 attenuated fibrotic responses of renal epithelia to TGF-β1 exposure; and silencing of TGFBI induced expression of the epithelial cell marker - E-cadherin. We identified low abundance transcripts in sequence data and validated expression levels of several transcripts (ANKRD56, ENTPD8) in tubular enriched kidney biopsies of DN patients versus living donors. In conclusion, we have defined a TGF-β1-driven pro-fibrotic signal in renal epithelial cells that is also evident in the DN renal transcriptome.

KW - Blotting, Western

KW - Cell Line

KW - Diabetic Nephropathies

KW - Epithelial Cells

KW - Gene Expression Profiling

KW - Humans

KW - Kidney

KW - Polymerase Chain Reaction

KW - Transforming Growth Factor beta1

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.bbadis.2012.01.008

DO - 10.1016/j.bbadis.2012.01.008

M3 - SCORING: Journal article

C2 - 22266139

VL - 1822

SP - 589

EP - 599

JO - Biochim Biophys Acta

JF - Biochim Biophys Acta

SN - 0006-3002

IS - 4

ER -