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Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS

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Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS. / Li, Jinhua; Sun, Yu Bo Yang; Chen, Weiyi; Fan, Jinjin; Li, Songhui; Qu, Xinli; Chen, Qikang; Chen, Riling; Zhu, Dajian; Zhang, Jinfeng; Wu, Zhuguo; Chi, Honggang; Crawford, Simon; Oorschot, Viola; Puelles, Victor G; Kerr, Peter G; Ren, Yi; Nilsson, Susan K; Christian, Mark; Tang, Huanwen; Chen, Wei; Bertram, John F; Nikolic-Paterson, David J; Yu, Xueqing.

In: EMBO REP, Vol. 21, No. 2, 05.02.2020, p. e48781.

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

Harvard

Li, J, Sun, YBY, Chen, W, Fan, J, Li, S, Qu, X, Chen, Q, Chen, R, Zhu, D, Zhang, J, Wu, Z, Chi, H, Crawford, S, Oorschot, V, Puelles, VG, Kerr, PG, Ren, Y, Nilsson, SK, Christian, M, Tang, H, Chen, W, Bertram, JF, Nikolic-Paterson, DJ & Yu, X 2020, 'Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS', EMBO REP, vol. 21, no. 2, pp. e48781. https://doi.org/10.15252/embr.201948781

APA

Li, J., Sun, Y. B. Y., Chen, W., Fan, J., Li, S., Qu, X., Chen, Q., Chen, R., Zhu, D., Zhang, J., Wu, Z., Chi, H., Crawford, S., Oorschot, V., Puelles, V. G., Kerr, P. G., Ren, Y., Nilsson, S. K., Christian, M., ... Yu, X. (2020). Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS. EMBO REP, 21(2), e48781. https://doi.org/10.15252/embr.201948781

Vancouver

Li J, Sun YBY, Chen W, Fan J, Li S, Qu X et al. Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS. EMBO REP. 2020 Feb 5;21(2):e48781. https://doi.org/10.15252/embr.201948781

Bibtex

@article{faa73ada0f714ff185f117ba1a1728d7,
title = "Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS",
abstract = "Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.",
author = "Jinhua Li and Sun, {Yu Bo Yang} and Weiyi Chen and Jinjin Fan and Songhui Li and Xinli Qu and Qikang Chen and Riling Chen and Dajian Zhu and Jinfeng Zhang and Zhuguo Wu and Honggang Chi and Simon Crawford and Viola Oorschot and Puelles, {Victor G} and Kerr, {Peter G} and Yi Ren and Nilsson, {Susan K} and Mark Christian and Huanwen Tang and Wei Chen and Bertram, {John F} and Nikolic-Paterson, {David J} and Xueqing Yu",
note = "{\textcopyright} 2020 The Authors.",
year = "2020",
month = feb,
day = "5",
doi = "10.15252/embr.201948781",
language = "English",
volume = "21",
pages = "e48781",
journal = "EMBO REP",
issn = "1469-221X",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS

AU - Li, Jinhua

AU - Sun, Yu Bo Yang

AU - Chen, Weiyi

AU - Fan, Jinjin

AU - Li, Songhui

AU - Qu, Xinli

AU - Chen, Qikang

AU - Chen, Riling

AU - Zhu, Dajian

AU - Zhang, Jinfeng

AU - Wu, Zhuguo

AU - Chi, Honggang

AU - Crawford, Simon

AU - Oorschot, Viola

AU - Puelles, Victor G

AU - Kerr, Peter G

AU - Ren, Yi

AU - Nilsson, Susan K

AU - Christian, Mark

AU - Tang, Huanwen

AU - Chen, Wei

AU - Bertram, John F

AU - Nikolic-Paterson, David J

AU - Yu, Xueqing

N1 - © 2020 The Authors.

PY - 2020/2/5

Y1 - 2020/2/5

N2 - Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.

AB - Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.

U2 - 10.15252/embr.201948781

DO - 10.15252/embr.201948781

M3 - SCORING: Journal article

C2 - 31916354

VL - 21

SP - e48781

JO - EMBO REP

JF - EMBO REP

SN - 1469-221X

IS - 2

ER -