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Jens Randel Nyengaard

Differential effects of Smad3 targeting in a murine model of chronic kidney disease

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Differential effects of Smad3 targeting in a murine model of chronic kidney disease. / Kellenberger, Terese; Krag, Søren; Danielsen, Carl Christian; Wang, Xiao-Fan; Nyengaard, Jens Randel; Pedersen, Lea Hougaard; Yang, Chuanxu; Gao, Shan; Wogensen, Lise.

In: Physiological Reports, Vol. 1, No. 7, e00181, 01.12.2013.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Kellenberger, T, Krag, S, Danielsen, CC, Wang, X-F, Nyengaard, JR, Pedersen, LH, Yang, C, Gao, S & Wogensen, L 2013, 'Differential effects of Smad3 targeting in a murine model of chronic kidney disease', Physiological Reports, vol. 1, no. 7, e00181. https://doi.org/10.1002/phy2.181

APA

Kellenberger, T., Krag, S., Danielsen, C. C., Wang, X-F., Nyengaard, J. R., Pedersen, L. H., Yang, C., Gao, S., & Wogensen, L. (2013). Differential effects of Smad3 targeting in a murine model of chronic kidney disease. Physiological Reports, 1(7), [e00181]. https://doi.org/10.1002/phy2.181

CBE

Kellenberger T, Krag S, Danielsen CC, Wang X-F, Nyengaard JR, Pedersen LH, Yang C, Gao S, Wogensen L. 2013. Differential effects of Smad3 targeting in a murine model of chronic kidney disease. Physiological Reports. 1(7):Article e00181. https://doi.org/10.1002/phy2.181

MLA

Vancouver

Kellenberger T, Krag S, Danielsen CC, Wang X-F, Nyengaard JR, Pedersen LH et al. Differential effects of Smad3 targeting in a murine model of chronic kidney disease. Physiological Reports. 2013 Dec 1;1(7). e00181. https://doi.org/10.1002/phy2.181

Author

Kellenberger, Terese ; Krag, Søren ; Danielsen, Carl Christian ; Wang, Xiao-Fan ; Nyengaard, Jens Randel ; Pedersen, Lea Hougaard ; Yang, Chuanxu ; Gao, Shan ; Wogensen, Lise. / Differential effects of Smad3 targeting in a murine model of chronic kidney disease. In: Physiological Reports. 2013 ; Vol. 1, No. 7.

Bibtex

@article{f7fb1ac47ad9492eaaeff27002c4d733,
title = "Differential effects of Smad3 targeting in a murine model of chronic kidney disease",
abstract = "Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role in transcriptional regulation of target genes involved in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that blockade of Smad3 attenuates the development of TGF-β1-driven renal fibrosis. This was examined in vivo in a transgenic model of TGF-β1-induced chronic kidney disease with Smad3 or without Smad3 expression and in vitro in mesangial cells and glomerular endothelial cells with Smad2/3 inhibitors or Smad3-knockdown. Electron microscopy was used for evaluation of morphological changes, real-time polymerase chain reaction for detection of RNA expression, and immunohistochemistry for localization of ECM components. Matrix metalloproteinase (MMP) level was assessed by gelatin zymography electrophoresis and located by in situ zymography. The results show TGF-β1-induced mesangial matrix expansion, tubulointerstitial fibrosis, and tubular basement membrane thickening that are attenuated by Smad3 deletion, whereas TGF-β1-induced glomerular basement membrane thickening is not shown. The amount and distribution profile of MMP-2 may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in different cell types in the kidney.",
author = "Terese Kellenberger and S{\o}ren Krag and Danielsen, {Carl Christian} and Xiao-Fan Wang and Nyengaard, {Jens Randel} and Pedersen, {Lea Hougaard} and Chuanxu Yang and Shan Gao and Lise Wogensen",
year = "2013",
month = dec,
day = "1",
doi = "10.1002/phy2.181",
language = "English",
volume = "1",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "Wiley Periodicals, Inc.",
number = "7",

}

RIS

TY - JOUR

T1 - Differential effects of Smad3 targeting in a murine model of chronic kidney disease

AU - Kellenberger, Terese

AU - Krag, Søren

AU - Danielsen, Carl Christian

AU - Wang, Xiao-Fan

AU - Nyengaard, Jens Randel

AU - Pedersen, Lea Hougaard

AU - Yang, Chuanxu

AU - Gao, Shan

AU - Wogensen, Lise

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role in transcriptional regulation of target genes involved in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that blockade of Smad3 attenuates the development of TGF-β1-driven renal fibrosis. This was examined in vivo in a transgenic model of TGF-β1-induced chronic kidney disease with Smad3 or without Smad3 expression and in vitro in mesangial cells and glomerular endothelial cells with Smad2/3 inhibitors or Smad3-knockdown. Electron microscopy was used for evaluation of morphological changes, real-time polymerase chain reaction for detection of RNA expression, and immunohistochemistry for localization of ECM components. Matrix metalloproteinase (MMP) level was assessed by gelatin zymography electrophoresis and located by in situ zymography. The results show TGF-β1-induced mesangial matrix expansion, tubulointerstitial fibrosis, and tubular basement membrane thickening that are attenuated by Smad3 deletion, whereas TGF-β1-induced glomerular basement membrane thickening is not shown. The amount and distribution profile of MMP-2 may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in different cell types in the kidney.

AB - Transforming growth factor (TGF)-β1 has a pivotal role in the pathogenesis of progressive kidney diseases that are characterized by fibrosis. The main intracellular signaling pathway of TGF-β1 is the Smad system, where Smad2 and Smad3 play a central role in transcriptional regulation of target genes involved in extracellular matrix (ECM) metabolism. This study analyzes the hypothesis that blockade of Smad3 attenuates the development of TGF-β1-driven renal fibrosis. This was examined in vivo in a transgenic model of TGF-β1-induced chronic kidney disease with Smad3 or without Smad3 expression and in vitro in mesangial cells and glomerular endothelial cells with Smad2/3 inhibitors or Smad3-knockdown. Electron microscopy was used for evaluation of morphological changes, real-time polymerase chain reaction for detection of RNA expression, and immunohistochemistry for localization of ECM components. Matrix metalloproteinase (MMP) level was assessed by gelatin zymography electrophoresis and located by in situ zymography. The results show TGF-β1-induced mesangial matrix expansion, tubulointerstitial fibrosis, and tubular basement membrane thickening that are attenuated by Smad3 deletion, whereas TGF-β1-induced glomerular basement membrane thickening is not shown. The amount and distribution profile of MMP-2 may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in different cell types in the kidney.

U2 - 10.1002/phy2.181

DO - 10.1002/phy2.181

M3 - Journal article

C2 - 24744860

VL - 1

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 7

M1 - e00181

ER -