PortalPublikationenBAMBI elimination enhances alternative TGF-β signaling and g...

BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice

Standard

BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice. / Fan, Ying; Li, Xuezhu; Xiao, Wenzhen; Fu, Jia; Harris, Ray C; Lindenmeyer, Maja; Cohen, Clemens D; Guillot, Nicolas; Baron, Margaret H; Wang, Niansong; Lee, Kyung; He, John C; Schlondorff, Detlef; Chuang, Peter Y.

in: DIABETES, Jahrgang 64, Nr. 6, 06.2015, S. 2220-33.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fan, Y, Li, X, Xiao, W, Fu, J, Harris, RC, Lindenmeyer, M, Cohen, CD, Guillot, N, Baron, MH, Wang, N, Lee, K, He, JC, Schlondorff, D & Chuang, PY 2015, 'BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice', DIABETES, Jg. 64, Nr. 6, S. 2220-33. https://doi.org/10.2337/db14-1397

APA

Fan, Y., Li, X., Xiao, W., Fu, J., Harris, R. C., Lindenmeyer, M., Cohen, C. D., Guillot, N., Baron, M. H., Wang, N., Lee, K., He, J. C., Schlondorff, D., & Chuang, P. Y. (2015). BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice. DIABETES, 64(6), 2220-33. https://doi.org/10.2337/db14-1397

Vancouver

Fan Y, Li X, Xiao W, Fu J, Harris RC, Lindenmeyer M et al. BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice. DIABETES. 2015 Jun;64(6):2220-33. https://doi.org/10.2337/db14-1397

Bibtex

@article{70e2fd6b13f94a74bc3eab04269f24ae,
title = "BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice",
abstract = "BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the transforming growth factor (TGF)-β type I receptor family and a negative modulator of TGF-β kinase signaling, and BAMBI(-/-) mice show mild endothelial dysfunction. Because diabetic glomerular disease is associated with TGF-β overexpression and microvascular alterations, we examined the effect of diabetes on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in glomeruli from mice with type 2 diabetes, BAMBI was downregulated. We then examined the effects of BAMBI deletion on streptozotocin-induced diabetic glomerulopathy in mice. BAMBI(-/-) mice developed more albuminuria, with a widening of foot processes, than BAMBI(+/+) mice, along with increased activation of alternative TGF-β pathways such as extracellular signal-related kinase (ERK)1/2 and Smad1/5 in glomeruli and cortices of BAMBI(-/-) mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability, were downmodulated in glomeruli from BAMBI(-/-) mice with diabetes. Incubation of glomeruli from nondiabetic BAMBI(+/+) or BAMBI(-/-) mice with TGF-β resulted in the downregulation of Vegfr2 and Angpt1, effects that were more pronounced in BAMBI(-/-) mice and were prevented by a MEK inhibitor. The downregulation of Vegfr2 in diabetes was localized to glomerular endothelial cells using a histone yellow reporter under the Vegfr2 promoter. Thus, BAMBI modulates the effects of diabetes on glomerular permselectivity in association with altered ERK1/2 and Smad1/5 signaling. Future therapeutic interventions with inhibitors of alternative TGF-β signaling may therefore be of interest in diabetic nephropathy.",
keywords = "Angiopoietin-1, Animals, Blotting, Western, Humans, In Vitro Techniques, Kidney Glomerulus, Membrane Proteins, Mice, Signal Transduction, Smad1 Protein, Smad5 Protein, Transforming Growth Factor beta, Vascular Endothelial Growth Factor Receptor-2, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.",
author = "Ying Fan and Xuezhu Li and Wenzhen Xiao and Jia Fu and Harris, {Ray C} and Maja Lindenmeyer and Cohen, {Clemens D} and Nicolas Guillot and Baron, {Margaret H} and Niansong Wang and Kyung Lee and He, {John C} and Detlef Schlondorff and Chuang, {Peter Y}",
note = "{\textcopyright} 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2015",
month = jun,
doi = "10.2337/db14-1397",
language = "English",
volume = "64",
pages = "2220--33",
journal = "DIABETES",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice

AU - Fan, Ying

AU - Li, Xuezhu

AU - Xiao, Wenzhen

AU - Fu, Jia

AU - Harris, Ray C

AU - Lindenmeyer, Maja

AU - Cohen, Clemens D

AU - Guillot, Nicolas

AU - Baron, Margaret H

AU - Wang, Niansong

AU - Lee, Kyung

AU - He, John C

AU - Schlondorff, Detlef

AU - Chuang, Peter Y

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2015/6

Y1 - 2015/6

N2 - BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the transforming growth factor (TGF)-β type I receptor family and a negative modulator of TGF-β kinase signaling, and BAMBI(-/-) mice show mild endothelial dysfunction. Because diabetic glomerular disease is associated with TGF-β overexpression and microvascular alterations, we examined the effect of diabetes on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in glomeruli from mice with type 2 diabetes, BAMBI was downregulated. We then examined the effects of BAMBI deletion on streptozotocin-induced diabetic glomerulopathy in mice. BAMBI(-/-) mice developed more albuminuria, with a widening of foot processes, than BAMBI(+/+) mice, along with increased activation of alternative TGF-β pathways such as extracellular signal-related kinase (ERK)1/2 and Smad1/5 in glomeruli and cortices of BAMBI(-/-) mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability, were downmodulated in glomeruli from BAMBI(-/-) mice with diabetes. Incubation of glomeruli from nondiabetic BAMBI(+/+) or BAMBI(-/-) mice with TGF-β resulted in the downregulation of Vegfr2 and Angpt1, effects that were more pronounced in BAMBI(-/-) mice and were prevented by a MEK inhibitor. The downregulation of Vegfr2 in diabetes was localized to glomerular endothelial cells using a histone yellow reporter under the Vegfr2 promoter. Thus, BAMBI modulates the effects of diabetes on glomerular permselectivity in association with altered ERK1/2 and Smad1/5 signaling. Future therapeutic interventions with inhibitors of alternative TGF-β signaling may therefore be of interest in diabetic nephropathy.

AB - BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the transforming growth factor (TGF)-β type I receptor family and a negative modulator of TGF-β kinase signaling, and BAMBI(-/-) mice show mild endothelial dysfunction. Because diabetic glomerular disease is associated with TGF-β overexpression and microvascular alterations, we examined the effect of diabetes on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in glomeruli from mice with type 2 diabetes, BAMBI was downregulated. We then examined the effects of BAMBI deletion on streptozotocin-induced diabetic glomerulopathy in mice. BAMBI(-/-) mice developed more albuminuria, with a widening of foot processes, than BAMBI(+/+) mice, along with increased activation of alternative TGF-β pathways such as extracellular signal-related kinase (ERK)1/2 and Smad1/5 in glomeruli and cortices of BAMBI(-/-) mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability, were downmodulated in glomeruli from BAMBI(-/-) mice with diabetes. Incubation of glomeruli from nondiabetic BAMBI(+/+) or BAMBI(-/-) mice with TGF-β resulted in the downregulation of Vegfr2 and Angpt1, effects that were more pronounced in BAMBI(-/-) mice and were prevented by a MEK inhibitor. The downregulation of Vegfr2 in diabetes was localized to glomerular endothelial cells using a histone yellow reporter under the Vegfr2 promoter. Thus, BAMBI modulates the effects of diabetes on glomerular permselectivity in association with altered ERK1/2 and Smad1/5 signaling. Future therapeutic interventions with inhibitors of alternative TGF-β signaling may therefore be of interest in diabetic nephropathy.

KW - Angiopoietin-1

KW - Animals

KW - Blotting, Western

KW - Humans

KW - In Vitro Techniques

KW - Kidney Glomerulus

KW - Membrane Proteins

KW - Mice

KW - Signal Transduction

KW - Smad1 Protein

KW - Smad5 Protein

KW - Transforming Growth Factor beta

KW - Vascular Endothelial Growth Factor Receptor-2

KW - Journal Article

KW - Research Support, N.I.H., Extramural

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

U2 - 10.2337/db14-1397

DO - 10.2337/db14-1397

M3 - SCORING: Journal article

C2 - 25576053

VL - 64

SP - 2220

EP - 2233

JO - DIABETES

JF - DIABETES

SN - 0012-1797

IS - 6

ER -