Matthias Kretzler

Personal Information
Title Professor
Expertise Nephropathy
Institution University of Michigan
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Grants/SubContracts 2
Progress Reports 2
Publications 28
Protocols 0
Committees 2

Murine-HumanTranscriptomic Comparisons in Diabetic Nephropathy and Neuropathy
Comparison of genome-wide transcriptional profiles obtained from human and murine diabetic nephropathy (DN) and polyneuropathy (DPN) should allow identification of diabetic endorgan damage mechanisms that are conserved between mice and humans as well as those that are important in humans but whose absence in mice impairs development of full-blown DN or DPN. Targeting these pathways should greatly facilitate translation of findings from animal models to human disease and the development of improved murine models of DN and DPN.
Cross-Species Systems Biology of Diabetic Nephropathy
Diabetic nephropathy (DN) is an endorgan complication responsible for significant morbidity and mortality in type 1 and type 2 diabetes mellitus. Association of genes and gene products with DN are currently defined in humans using genome wide association studies and renal tissue based gene expression studies. However, animal models are instrumental to define the functional impact of the associated molecules. The AMDCC has established an extensive data set defining the framework for DN in mice. A crucial next step will be to integrate the murine molecular information with corresponding comprehensive human data sets. We have developed and employed a webbased analysis engine, Nephromine, for integrated systems biology analysis of renal gene expression for the renal research community. Nephromine accesses highly annotated human renal gene expression datasets in multiple search modes (see tutorial at, though Nephromine has been limited to human datasets to date. The goal of this application is to integrate murine DN gene expression data sets generated by the AMDCC and the renal research community at large with the human DN data sets to define shared and specific mechanism between mouse and man. Specific aims to be addressed are: Aim 1. Identify and annonate murine gene expression data sets of DN from AMDCC data repository, Gene Expression Omnibuts (GEO) and those accessed by direct interaction with investigative teams. Aim 2. Compare murine DN gene expression data sets with human DN data sets and identify shared transcriptional changes on a network level. Aim 3. Upload murine data sets into Nephromine for human-mouse comparative analysis by the renal research community. Comparing the renal transcriptiome of human DN to the carefully characterized AMDCC murine DN models will allow the renal research community to define molecular mechanism shared between mouse and man. With this information, investigators will be able to select the murine models that recapitulate the human disease mechanisms to be interrogated in their murine experimental studies. Defining mouse models a priori for their ability to recapitulate human disease will be a crucial step to increase comparability of murine studies to human disease mechanisms. This will aid in defining novel therapeutic targets for their efficacy in the specific murine models of DN and should decrease the attrition rate of compounds with activity in murine DN in their further validation as therapeutic targets of human DN.

Progress Reports

Annual Reports
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Year: 2017; Items: 2

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.
Hinder LM, Park M, Rumora AE, Hur J, Eichinger F, Pennathur S, Kretzler M, Brosius FC, Feldman EL
Journal of cellular and molecular medicine, 2017
Podocyte-specific JAK2 overexpression worsens diabetic kidney disease in mice.
Zhang H, Nair V, Saha J, Atkins KB, Hodgin JB, Saunders TL, Myers MG, Werner T, Kretzler M, Brosius FC
Kidney international, 2017

Year: 2016; Items: 3

JAK inhibition in the treatment of diabetic kidney disease.
Brosius FC, Tuttle KR, Kretzler M
Diabetologia, 2016 (59), 1624 - 7
Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury.
Pedigo CE, Ducasa GM, Leclercq F, Sloan A, Mitrofanova A, Hashmi T, Molina-David J, Ge M, Lassenius MI, Forsblom C, Lehto M, Groop PH, Kretzler M, Eddy S, Martini S, Reich H, Wahl P, Ghiggeri G, Faul C, Burke GW, Kretz O, Huber TB, Mendez AJ, Merscher S, Fornoni A
The Journal of clinical investigation, 2016 (126), 3336 - 50
Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications.
Sas KM, Kayampilly P, Byun J, Nair V, Hinder LM, Hur J, Zhang H, Lin C, Qi NR, Michailidis G, Groop PH, Nelson RG, Darshi M, Sharma K, Schelling JR, Sedor JR, Pop-Busui R, Weinberg JM, Soleimanpour SA, Abcouwer SF, Gardner TW, Burant CF, Feldman EL, Kretzler M, Brosius FC, Pennathur S
JCI insight, 2016 (1), e86976

Year: 2015; Items: 1

Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease.
Yoo TH, Pedigo CE, Guzman J, Correa-Medina M, Wei C, Villarreal R, Mitrofanova A, Leclercq F, Faul C, Li J, Kretzler M, Nelson RG, Lehto M, Forsblom C, Groop PH, Reiser J, Burke GW, Fornoni A, Merscher S
Journal of the American Society of Nephrology : JASN, 2015 (26), 133 - 47

Year: 2014; Items: 1

MicroRNA-21 in Glomerular Injury.
Lai JY, Luo J, O'Connor C, Jing X, Nair V, Ju W, Randolph A, Ben-Dov IZ, Matar RN, Briskin D, Zavadil J, Nelson RG, Tuschl T, Brosius FC, Kretzler M, Bitzer M
Journal of the American Society of Nephrology : JASN, 2014

Year: 2013; Items: 6

Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Hodgin JB, Nair V, Zhang H, Randolph A, Harris RC, Nelson RG, Weil EJ, Cavalcoli JD, Patel JM, Brosius FC, Kretzler M
Diabetes, 2013 (62), 299 - 308
From Single Nucleotide Polymorphism to Transcriptional Mechanism: A Model for FRMD3 in Diabetic Nephropathy.
Martini S, Nair V, Patel SR, Eichinger F, Nelson RG, Weil EJ, Pezzolesi MG, Krolewski AS, Randolph A, Keller BJ, Werner T, Kretzler M
Diabetes, 2013 (62), 2605 - 2612
Transcriptome analysis of proximal tubular cells (HK-2) exposed to urines of type 1 diabetes patients at risk of early progressive renal function decline.
Wanic K, Krolewski B, Ju W, Placha G, Niewczas MA, Walker W, Warram JH, Kretzler M, Krolewski AS
PLoS ONE, 2013 (8), e57751
Submitted Externally
Diabetic Nephropathy: A National Dialogue.
Breyer MD, Coffman TM, Flessner MF, Fried LF, Harris RC, Ketchum CJ, Kretzler M, Nelson RG, Sedor JR, Susztak K, on behalf of the Kidney Research National Dialogue (KRND)
Clinical journal of the American Society of Nephrology : CJASN, 2013
Cyclodextrin protects podocytes in diabetic kidney disease.
Merscher-Gomez S, Guzman J, Pedigo CE, Lehto M, Aguillon-Prada R, Mendez A, Lassenius MI, Forsblom C, Yoo T, Villarreal R, Maiguel D, Johnson K, Goldberg R, Nair V, Randolph A, Kretzler M, Nelson RG, Burke GW, Groop PH, Fornoni A
Diabetes, 2013 (62), 3817 - 3827
Targeted Glomerular Angiopoietin-1 Therapy for Early Diabetic Kidney Disease.
Dessapt-Baradez C, Woolf AS, White KE, Pan J, Huang JL, Hayward AA, Price KL, Kolatsi-Joannou M, Locatelli M, Diennet M, Webster Z, Smillie SJ, Nair V, Kretzler M, Cohen CD, Long DA, Gnudi L
Journal of the American Society of Nephrology : JASN, 2013 (25), 33 - 42
Submitted Externally

Year: 2012; Items: 2

Bcl-2-modifying factor induces renal proximal tubular cell apoptosis in diabetic mice.
Lau GJ, Godin N, Maachi H, Lo CS, Wu SJ, Zhu JX, Brezniceanu ML, Chénier I, Fragasso-Marquis J, Lattouf JB, Ethier J, Filep JG, Ingelfinger JR, Nair V, Kretzler M, Cohen CD, Zhang SL, Chan JS
Diabetes, 2012 (61), 474 - 484
Perspectives on systems biology applications in diabetic kidney disease.
Komorowsky CV, Brosius FC, Pennathur S, Kretzler M
Journal of cardiovascular translational research, 2012 (5), 491 - 508

Year: 2011; Items: 4

Role of mTOR in podocyte function and diabetic nephropathy in humans and mice.
Gödel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S, Debreczeni-Mór A, Lindenmeyer MT, Rastaldi MP, Hartleben G, Wiech T, Fornoni A, Nelson RG, Kretzler M, Wanke R, Pavenstädt H, Kerjaschki D, Cohen CD, Hall MN, Rüegg MA, Inoki K, Walz G, Huber TB
The Journal of clinical investigation, 2011 (121), 2197 - 2209
mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice.
Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, Blattner SM, Ikenoue T, Rüegg MA, Hall MN, Kwiatkowski DJ, Rastaldi MP, Huber TB, Kretzler M, Holzman LB, Wiggins RC, Guan KL
The Journal of clinical investigation, 2011 (121), 2181 - 2196
Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus.
Chuang PY, Dai Y, Liu R, He H, Kretzler M, Jim B, Cohen CD, He JC
PLoS ONE, 2011 (6), e23566
The identification of gene expression profiles associated with progression of human diabetic neuropathy.
Hur J, Sullivan KA, Pande M, Hong Y, Sima AA, Jagadish HV, Kretzler M, Feldman EL
Brain : a journal of neurology, 2011 (134), 3222 - 3235

Year: 2010; Items: 1

The management of diabetic neuropathy in CKD.
Pop-Busui R, Roberts L, Pennathur S, Kretzler M, Brosius FC, Feldman EL
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2010 (55), 365 - 385

Year: 2009; Items: 2

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
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

Year: 2008; Items: 6

From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy.
Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius FC
Diabetes, 2008 (57(6)), 1439 - 1445
Rosiglitazone Treatment Reduces Diabetic Neuropathy in STZ treated DBA/2J mice
Timothy D Wiggin, Matthias Kretzler, Subramaniam Pennathur, Kelli A. Sullivan, Frank C Brosius, Eva L Feldman
Endocrinology, 2008 (149(10)), 4928 - 4937
Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy
Hongyu Zhang, Jharna Saha, MaryLee Schin, Jaeman Byun, Matthias Kretzler, Eva L. Feldman, David A. Weild, Subramaniam Pennathur, Frank C. Brosius III
American journal of physiology. Renal physiology, 2008 (295(4)), F1071 - F1081
Improved elucidation of biological processes linked to diabetic nephropathy by single probe-based microarray data analysis.
Cohen CD, Lindenmeyer MT, Eichinger F, Hahn A, Seifert M, Moll AG, Schmid H, Kiss E, Gröne E, Gröne HJ, Kretzler M, Werner T, Nelson PJ
PLoS ONE, 2008 (3), e2937
Submitted Externally
Defining human diabetic nephropathy on the molecular level: integration of transcriptomic profiles with biological knowledge.
Martini S, Eichinger F, Nair V, Kretzler M
Reviews in endocrine & metabolic disorders, 2008 (9), 267 - 274
Enhanced Expression of JAK-STAT Pathway Members in Human Diabetic Nephropathy
Celine C. Berthier, PhD., Hongyu Zhang, M.D., MaryLee Schin, B.S., Anna Henger, PhD, Robert G. Nelson, M.D., PhD, Berne Yee, M.D., Anissa Boucherot, PhD., Christin Carter-Su, PhD., Lawrence S. Argetsinger, PhD., Maria Pia Rastaldi, M.D., Frank C. Brosius, M.D., Matthias Kretzler, M.D
Diabetes, 2008 (Epub), 469 - 477
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