Research ExplorerPublicationsDysregulated mesenchymal PDGFR-β drives kidney fibrosis

Dysregulated mesenchymal PDGFR-β drives kidney fibrosis

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Dysregulated mesenchymal PDGFR-β drives kidney fibrosis. / Buhl, Eva M; Djudjaj, Sonja; Klinkhammer, Barbara M; Ermert, Katja; Puelles, Victor G; Lindenmeyer, Maja T; Cohen, Clemens D; He, Chaoyong; Borkham-Kamphorst, Erawan; Weiskirchen, Ralf; Denecke, Bernd; Trairatphisan, Panuwat; Saez-Rodriguez, Julio; Huber, Tobias B; Olson, Lorin E; Floege, Jürgen; Boor, Peter.

In: EMBO MOL MED, Vol. 12, No. 3, 06.03.2020, p. e11021.

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

Harvard

Buhl, EM, Djudjaj, S, Klinkhammer, BM, Ermert, K, Puelles, VG, Lindenmeyer, MT, Cohen, CD, He, C, Borkham-Kamphorst, E, Weiskirchen, R, Denecke, B, Trairatphisan, P, Saez-Rodriguez, J, Huber, TB, Olson, LE, Floege, J & Boor, P 2020, 'Dysregulated mesenchymal PDGFR-β drives kidney fibrosis', EMBO MOL MED, vol. 12, no. 3, pp. e11021. https://doi.org/10.15252/emmm.201911021

APA

Buhl, E. M., Djudjaj, S., Klinkhammer, B. M., Ermert, K., Puelles, V. G., Lindenmeyer, M. T., Cohen, C. D., He, C., Borkham-Kamphorst, E., Weiskirchen, R., Denecke, B., Trairatphisan, P., Saez-Rodriguez, J., Huber, T. B., Olson, L. E., Floege, J., & Boor, P. (2020). Dysregulated mesenchymal PDGFR-β drives kidney fibrosis. EMBO MOL MED, 12(3), e11021. https://doi.org/10.15252/emmm.201911021

Vancouver

Buhl EM, Djudjaj S, Klinkhammer BM, Ermert K, Puelles VG, Lindenmeyer MT et al. Dysregulated mesenchymal PDGFR-β drives kidney fibrosis. EMBO MOL MED. 2020 Mar 6;12(3):e11021. https://doi.org/10.15252/emmm.201911021

Bibtex

@article{3422248d3b694b539cbef0df2279684c,
title = "Dysregulated mesenchymal PDGFR-β drives kidney fibrosis",
abstract = "Kidney fibrosis is characterized by expansion and activation of platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells. To study the consequences of PDGFR-β activation, we developed a model of primary renal fibrosis using transgenic mice with PDGFR-β activation specifically in renal mesenchymal cells, driving their pathological proliferation and phenotypic switch toward myofibroblasts. This resulted in progressive mesangioproliferative glomerulonephritis, mesangial sclerosis, and interstitial fibrosis with progressive anemia due to loss of erythropoietin production by fibroblasts. Fibrosis induced secondary tubular epithelial injury at later stages, coinciding with microinflammation, and aggravated the progression of hypertensive and obstructive nephropathy. Inhibition of PDGFR activation reversed fibrosis more effectively in the tubulointerstitium compared to glomeruli. Gene expression signatures in mice with PDGFR-β activation resembled those found in patients. In conclusion, PDGFR-β activation alone is sufficient to induce progressive renal fibrosis and failure, mimicking key aspects of chronic kidney disease in humans. Our data provide direct proof that fibrosis per se can drive chronic organ damage and establish a model of primary fibrosis allowing specific studies targeting fibrosis progression and regression.",
author = "Buhl, {Eva M} and Sonja Djudjaj and Klinkhammer, {Barbara M} and Katja Ermert and Puelles, {Victor G} and Lindenmeyer, {Maja T} and Cohen, {Clemens D} and Chaoyong He and Erawan Borkham-Kamphorst and Ralf Weiskirchen and Bernd Denecke and Panuwat Trairatphisan and Julio Saez-Rodriguez and Huber, {Tobias B} and Olson, {Lorin E} and J{\"u}rgen Floege and Peter Boor",
note = "{\textcopyright} 2020 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2020",
month = mar,
day = "6",
doi = "10.15252/emmm.201911021",
language = "English",
volume = "12",
pages = "e11021",
journal = "EMBO MOL MED",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Dysregulated mesenchymal PDGFR-β drives kidney fibrosis

AU - Buhl, Eva M

AU - Djudjaj, Sonja

AU - Klinkhammer, Barbara M

AU - Ermert, Katja

AU - Puelles, Victor G

AU - Lindenmeyer, Maja T

AU - Cohen, Clemens D

AU - He, Chaoyong

AU - Borkham-Kamphorst, Erawan

AU - Weiskirchen, Ralf

AU - Denecke, Bernd

AU - Trairatphisan, Panuwat

AU - Saez-Rodriguez, Julio

AU - Huber, Tobias B

AU - Olson, Lorin E

AU - Floege, Jürgen

AU - Boor, Peter

N1 - © 2020 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2020/3/6

Y1 - 2020/3/6

N2 - Kidney fibrosis is characterized by expansion and activation of platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells. To study the consequences of PDGFR-β activation, we developed a model of primary renal fibrosis using transgenic mice with PDGFR-β activation specifically in renal mesenchymal cells, driving their pathological proliferation and phenotypic switch toward myofibroblasts. This resulted in progressive mesangioproliferative glomerulonephritis, mesangial sclerosis, and interstitial fibrosis with progressive anemia due to loss of erythropoietin production by fibroblasts. Fibrosis induced secondary tubular epithelial injury at later stages, coinciding with microinflammation, and aggravated the progression of hypertensive and obstructive nephropathy. Inhibition of PDGFR activation reversed fibrosis more effectively in the tubulointerstitium compared to glomeruli. Gene expression signatures in mice with PDGFR-β activation resembled those found in patients. In conclusion, PDGFR-β activation alone is sufficient to induce progressive renal fibrosis and failure, mimicking key aspects of chronic kidney disease in humans. Our data provide direct proof that fibrosis per se can drive chronic organ damage and establish a model of primary fibrosis allowing specific studies targeting fibrosis progression and regression.

AB - Kidney fibrosis is characterized by expansion and activation of platelet-derived growth factor receptor-β (PDGFR-β)-positive mesenchymal cells. To study the consequences of PDGFR-β activation, we developed a model of primary renal fibrosis using transgenic mice with PDGFR-β activation specifically in renal mesenchymal cells, driving their pathological proliferation and phenotypic switch toward myofibroblasts. This resulted in progressive mesangioproliferative glomerulonephritis, mesangial sclerosis, and interstitial fibrosis with progressive anemia due to loss of erythropoietin production by fibroblasts. Fibrosis induced secondary tubular epithelial injury at later stages, coinciding with microinflammation, and aggravated the progression of hypertensive and obstructive nephropathy. Inhibition of PDGFR activation reversed fibrosis more effectively in the tubulointerstitium compared to glomeruli. Gene expression signatures in mice with PDGFR-β activation resembled those found in patients. In conclusion, PDGFR-β activation alone is sufficient to induce progressive renal fibrosis and failure, mimicking key aspects of chronic kidney disease in humans. Our data provide direct proof that fibrosis per se can drive chronic organ damage and establish a model of primary fibrosis allowing specific studies targeting fibrosis progression and regression.

U2 - 10.15252/emmm.201911021

DO - 10.15252/emmm.201911021

M3 - SCORING: Journal article

C2 - 31943786

VL - 12

SP - e11021

JO - EMBO MOL MED

JF - EMBO MOL MED

SN - 1757-4676

IS - 3

ER -