Erwin Bottinger

Personal Information
Title Professor
Expertise Nephropathy
Institution Mount Sinai School of Medicine
Data Summary
TypeCount
Grants/SubContracts 1
Progress Reports 8
Presentations 5
Publications 33
Protocols 0
Committees 1

Role and Mechanisms of Epithelial Injury in Diabetic Nephropathy
Grant Number: DK060995

Abstract: Glucotoxicity, lipotoxicity, advanced glycation end products (AGE), and reactive oxygen species (ROS) have emerged as important mediators of diabetes-induced tissue injury. However, the precise cellular targets and molecular mechanisms by which these mediators cause cellular injury in the kidney remain poorly defined. Both, glomerular (podocytes) and tubular epithelial cells are now emerging as important targets for diabetes-induced injury in diabetic nephropathy (DN). Thus, podocyte depletion has been described recently in humans with type 1 (T1DM) and type 2 (T2DM) diabetes, and is considered a strong predictor for the development of proteinuria. In addition, tubular epithelial apoptosis and epithelial-mesenchymal transition (EMT) may underlie the initiation of tubulointerstitial progression of DN. We present preliminary results that provide a compelling rationale to focus our research program on investigating the emerging role and mechanisms of epithelial cell injury in DN. Specifically, we will test two novel hypotheses: 1. The peroxisomal membrane proteins Mpv17l and/or Mpv17 are essential regulators of antioxidant defenses in glomerular podocytes and protect against diabetes-induced podocyte apoptosis and podocyte depletion (Bottinger, Mount Sinai); and 2. CD36 scavenger receptor for AGE and/or FFA is an essential mediator of AGE and/or FFA-induced tubular epithelial injury/apoptosis and tubulointerstitial progression of DN (Susztak, AECOM). The Specific Aims of this proposal are to test: 1. whether peroxisomal membrane proteins regulate antioxidant defense mechanisms in podocytes, and protect against ROS-mediated podocyte injury/apoptosis induced by diabetes 2. whether Mpv17-deficiency accelerates and increases podocyte apoptosis and depletion leading to progressive glomerulosclerosis and/or nodules in diabetic mouse models 3. which CD36-dependent intracellular pathways signal AGE and FFA induced tubular epithelial injury/apoptosis 4. whether proximal tubular overexpression of AGE binding proteins CD36 and RAGE leads to increased tubular epithelial injury/apoptosis and tubulointerstitial progression of DN in mice


Institution: Mount Sinai School of Medicine
One Gustave L. Levy Place
New York, NY
Fiscal Year:2006
Department:MEDICINE
Project Start: 9/30/2001
Project End: 8/31/2011
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Progress Reports

No funding program application progress reports found.

Annual Reports

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Bottinger, Erwin (2004)
2004Annual Report
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Bottinger, Erwin (2005)
2005Annual Report
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Bottinger, Erwin (2006)
2006Annual Report
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Bottinger, Erwin (2007)
2007Annual Report
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Bottinger, Erwin (2008)
2008Annual Report
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Bottinger, Erwin (2009)
2009Annual Report
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Bottinger, Erwin (2010)
2010Annual Report
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Bottinger, Erwin (2011)
2011Annual Report
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2014; Items: 4

 
Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis.
Daehn I, Casalena G, Zhang T, Shi S, Fenninger F, Barasch N, Yu L, D'Agati V, Schlondorff D, Kriz W, Haraldsson B, Bottinger EP
The Journal of clinical investigation, 2014 (124), 1608 - 1621
24590287
Published
 
Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro.
Casalena G, Krick S, Daehn I, Yu L, Ju W, Shi S, Tsai SY, D'Agati V, Lindenmeyer M, Cohen CD, Schlondorff D, Bottinger EP
American journal of physiology. Renal physiology, 2014 (306), F1372 - F1380
24598802
Published
 
Combinatorial actions of Tgfß and Activin ligands promote oligodendrocyte development and CNS myelination.
Dutta DJ, Zameer A, Mariani JN, Zhang J, Asp L, Huynh J, Mahase S, Laitman BM, Argaw AT, Mitiku N, Urbanski M, Melendez-Vasquez CV, Casaccia P, Hayot F, Bottinger EP, Brown CW, John GR
Development (Cambridge, England), 2014 (141), 2414 - 2428
Submitted Externally
24917498
Published
 
Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development.
Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K
Nature medicine, 2014 (21), 37 - 46
25419705
Published

Year: 2013; Items: 1

 
Smad2-dependent downregulation of miR-30 is required for TGF-ß-induced apoptosis in podocytes.
Shi S, Yu L, Zhang T, Qi H, Xavier S, Ju W, Bottinger E
PLoS ONE, 2013 (8), e75572
24086574
Published

Year: 2012; Items: 3

 
BAMBI regulates angiogenesis and endothelial homeostasis through modulation of alternative TGFß signaling.
Guillot N, Kollins D, Gilbert V, Xavier S, Chen J, Gentle M, Reddy A, Bottinger E, Jiang R, Rastaldi MP, Corbelli A, Schlondorff D
PLoS ONE, 2012 (7), e39406
Submitted Externally
22761782
Published
 
Transforming growth factor-ß, bioenergetics, and mitochondria in renal disease.
Casalena G, Daehn I, Bottinger E
Seminars in nephrology, 2012 (32), 295 - 303
22835461
Published
 
Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?
Gottesman O, Drill E, Lotay V, Bottinger E, Peter I
PLoS ONE, 2012 (7), e46419
23029515
Published

Year: 2011; Items: 1

 
Tracing the footsteps of glomerular insulin signaling in diabetic kidney disease.
Chang GY, Park AS, Susztak K
Kidney international, 2011 (79), 802 - 804
21451535
Published

Year: 2010; Items: 4

 
Lights on for aminopeptidases in cystic kidney disease.
Bottinger EP
The Journal of clinical investigation, 2010 (120), 660 - 663
20179346
Published
 
A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8.
Chua S, Li Y, Liu SM, Liu R, Chan KT, Martino J, Zheng Z, Susztak K, D'Agati VD, Gharavi AG
Kidney international, 2010
20520596
Published
 
Getting a notch closer to understanding diabetic kidney disease.
Ahn SH, Susztak K
Diabetes, 2010 (59), 1865 - 1867
Submitted Externally
20668292
Published
 
HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion.
Hoot KE, Oka M, Han G, Bottinger E, Zhang Q, Wang XJ
The Journal of clinical investigation, 2010 (120), 3606 - 3616
Submitted Externally
20852387
Published

Year: 2009; Items: 5

 
Laser capture microdissection of kidney tissue.
Woroniecki RP, Bottinger EP
Methods in molecular biology (Clifton, N.J.), 2009 (466), 73 - 82
19148600
Published
 
Human and murine kidneys show gender- and species-specific gene expression differences in response to injury.
Si H, Banga RS, Kapitsinou P, Ramaiah M, Lawrence J, Kambhampati G, Gruenwald A, Bottinger E, Glicklich D, Tellis V, Greenstein S, Thomas DB, Pullman J, Fazzari M, Susztak K
PLoS ONE, 2009 (4), e4802
19277126
Published
 
Renal gene and protein expression signatures for prediction of kidney disease progression.
Ju W, Eichinger F, Bitzer M, Oh J, McWeeney S, Berthier CC, Shedden K, Cohen CD, Henger A, Krick S, Kopp JB, Stoeckert CJ, Dikman S, Schröppel B, Thomas DB, Schlondorff D, Kretzler M, Bottinger EP
The American journal of pathology, 2009 (174(6)), 2073 - 2085
19465643
Published
 
TbetaRI independently activates Smad- and CD2AP-dependent pathways in podocytes.
Xavier S, Niranjan T, Krick S, Zhang T, Ju W, Shaw AS, Schiffer M, Bottinger EP
Journal of the American Society of Nephrology : JASN, 2009 (20), 2127 - 2137
19679673
Published
 
Mouse Models of Diabetic Nephropathy: A Midstream Analysis from the Diabetic Complications Consortium
Frank C. Brosius IIIa, Charles E. Alpersb, Erwin P. Bottingerc, Matthew D. Breyerd, ThomasM. Coffmane, Susan B. Gurleye, Raymond C. Harrisf, Masao Kakokig, Matthias Kretzler, Edward H. Leiterh, Moshe Levii, Richard A. McIndoej, Kumar Sharmak, Oliver Smithiesg, Katalin Susztakl, Nobuyuki Takahashig, Takamune Takahashif
Journal of the American Society of Nephrology : JASN, 2009 (20(12)), 2503 - 2512
19729434
Published

Year: 2008; Items: 3

 
Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis.
Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MP, Bottinger EP, Davidson A
Journal of immunology (Baltimore, Md. : 1950), 2008 (180), 1938 - 1947
Submitted Externally
18209092
Published
 
Mpv17l protects cells against mitochondrial dysfunction and apoptosis through its regulation of Omi/HtrA2
Stefanie Krick, Shaolin Shi, Wenjun Ju, Peter H Mundel and Erwin P Bottinger
Proceedings of the National Academy of Sciences of the United States of America, 2008 (105), 14106 - 14111
18772386
Published
 
Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis.
Shi S, Yu L, Chiu C, Sun Y, Chen J, Khitrov G, Merkenschlager M, Holzman LB, Zhang W, Mundel P, Bottinger EP
Journal of the American Society of Nephrology : JASN, 2008 (19(11)), 2159 - 2169
18776119
Published

Year: 2007; Items: 3

 
TGF-beta isoform signaling regulates secondary transition and mesenchymal-induced endocrine development in the embryonic mouse pancreas.
Tulachan SS, Tei E, Hembree M, Crisera C, Prasadan K, Koizumi M, Shah S, Guo P, Bottinger E, Gittes GK
Developmental biology, 2007 (305), 508 - 521
Submitted Externally
17418116
Published
 
TGF-beta in renal injury and disease.
Böttinger EP
Seminars in nephrology, 2007 (27(3)), 309 - 320
17533008
Published
 
Decorin Deficiency Enhances Progressive Nephropathy in Diabetic Mice
Kevin Jon Williams, Gang Qiu, Hitomi Katoaka Usui, Stephen R. Dunn, Peter McCue, Erwin Bottinger, Renato V. Iozzo, Kumar Sharma
The American journal of pathology, 2007 (171(5)), 1441 - 1450
17884968
Published

Year: 2006; Items: 3

 
Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy
Katalin Susztak, Amanda C. Raff, Mario Schiffer, Erwin P. Böttinger
Diabetes, 2006 (55), 225 - 233
16380497
Published
 
QTL MatchMaker: a multi-species quantitative trait loci (QTL) database and query system for annotation of genes and QTL.
Star KV, Song Q, Zhu A, Böttinger EP
Nucleic acids research, 2006 (34), D586 - D589
16381937
Published
 
Diabetic nephropathy: a frontier for personalized medicine.
Susztak K, Böttinger EP
Journal of the American Society of Nephrology : JASN, 2006 (17(2)), 361 - 367
16407421
Published

Year: 2005; Items: 4

 
Mouse Models of Diabetic Nephropathy
MATTHEW D. BREYER, ERWIN BÖTTINGER, FRANK C. BROSIUS, III, THOMAS M. COFFMAN, RAYMOND C. HARRIS, CHARLES W. HEILIG, AND KUMAR SHARMA (FOR THE AMDCC)
Journal of the American Society of Nephrology : JASN, 2005 (16), 27 - 45
15563560
Published
 
Multiple Metabolic Hits Converge on CD36 Scavenger Receptor as Novel Mediator of Tubular Epithelial Apoptosis in Diabetic Nephropathy
Katalin Susztak*, Emilio Ciccone†, Kumar Sharma†, ‡, Erwin P. Böttinger*, ‡
PLoS medicine / Public Library of Science, 2005 (2), 152 - 161
15737001
Published
 
Localization of the GLUT8 glucose transporter in murine kidney and regulation in vivo in nondiabetic and diabetic conditions.
Schiffer M, Susztak K, Ranalletta M, Raff AC, Böttinger EP, Charron MJ
American journal of physiology. Renal physiology, 2005 (289(1)), F186 - F193
15741607
Published
 
Use of GLUT-4 null mice to study skeletal muscle glucose uptake.
Charron MJ, Gorovits N, Laidlaw JS, Ranalletta M, Katz EB
Clinical and experimental pharmacology & physiology, 2005 (32(4)), 308 - 313
15810997
Published

Year: 2004; Items: 1

 
Molecular Profiling of Diabetic Mouse Kidneys Reveals Novel Genes Linked to Glomerular Disease
Katalin Susztak, Erwin Böttinger, Akiva Novetsky, Dan Liang, Yanqing Zhu, Emilio Ciccone, Dona Wu, Stephen Dunn, Peter McCue, Kumar Sharma
Diabetes, 2004 (53), 784 - 794
14988265
Published

Year: 2003; Items: 1

 
Genomic strategies for diabetic nephropathy.
Susztak K, Sharma K, Schiffer M, McCue P, Ciccone E, Böttinger EP
Journal of the American Society of Nephrology : JASN, 2003 (14), S271 - S278
12874445
Published

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Bottinger, Erwin (10/17/2005)
2005Presentation
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Bottinger, Erwin (2004)
2004Presentation
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Bottinger, Erwin (2006)
2006Presentation
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Bottinger, Erwin (2009)
2009Presentation
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Bottinger, Erwin (3/23/2005)
2005Presentation
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No protocols found.

No experiments found.