Kumar Sharma

Personal Information
Title Professor
Expertise Nephropathy
Institution University of California San Diego
Data Summary
TypeCount
Grants/SubContracts 3
Progress Reports 7
Presentations 3
Publications 43
Protocols 1
Committees 1
Experiments 0
Strains 1
Models 0

Adiponectin and Nox 4 in Diabetic Kidney Disease
Grant Number: DK076133

Abstract: During the first phase of the AMDCC our group at TJU studied the decorin KO diabetic mouse. Our hypothesis was that decorin acts as an endogenous protective factor by inhibiting active TGF-b. We found that decorin is indeed protective, as decorin KO mice had accelerated kidney disease and surprisingly increased mortality. Based on our results, the AMDCC investigators as a group chose the decorin KO diabetic mouse as a leading success during the 1st funding period. Of major mechanistic interest, we found that decorin KO diabetic mice that died exhibited evidence of renal insufficiency and low plasma adiponectin levels, months prior to mortality. This is similar to the human clinical condition. Low adiponectin levels are a powerful biomarker of increased cardiovascular morbidity and mortality in patients with kidney disease. Additionally, the decorin KO mice had increased NADPH oxidase (Nox4) expression in the kidney which may contribute to more severe nephropathy. In the next phase of the AMDCC, we propose test the following hypotheses. 1. Deficiency of adiponectin in combination with lack of decorin leads to enhanced lethality and diabetic nephropathy and 2. Increased Nox4 in vascular smooth muscle cells enhances diabetic nephropathy and the vascular complications of diabetic kidney disease. We propose to generate new diabetic mouse models by crossing adiponectin KO mice with decorin KO mice and by generating mice transgenic for smooth muscle Nox4 using the SM22 promoter. Diabetes will be induced by crossing with Akita mice. These mice will be characterized for diabetic nephropathy and cardiovascular disease. Both new models will be fully characterized for diabetic nephropathy. More importantly, we propose a series of interventional studies to test the causal role of TGF-b, adiponectin, and Nox4 in the pathogenesis of accelerated diabetic nephropathy. Key features we will focus on include matrix accumulation, renal function, autoregulation, and mortality. The proposed studies are directly related to the human condition, in which TGF-(, adiponectin, and Nox4 are key biomarkers for worse disease, but their pathogenetic role is unproven. Our findings will advance our mechanistic understanding of diabetic nephropathy and vascular disease and may lead to better biomarkers and novel treatments.


Institution: University of California San Diego
8950 Villa La Jolla Dr
La Jolla, CA
Fiscal Year:2006
Department:MEDICINE
Project Start: 9/30/2006
Project End: 8/31/2007
ICD: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

SubContract(s)


Diabetic Kidney and Nerve Disease with Hyperglycemia
Diabetic kidney and nerve disease in patients is associated with glycemia control. Initial studies revealed that mice with diabetes have a correlation with hyperglycemia and kidney disease. Int he present proposal we will determine if different mouse strains have different relationships between hyperglycemia and kidney and nerve disease and if gender is also an important variable.

Hyperglycemia and diabetic kidney and nerve disease
The proposed summer student application will seek to mine the AMDCC database to evaluate two key questions, 1. Does the degree of hyperglycemia correlate with the diabetic kidney and nerve complications, and 2. Are features of diabetic kidney and nerve disease track with each other? To answer these questions there will be a joint mentorship to guide several talented students for the summer period. Several new mouse models with diabetes have been developed by the AMDCC and their data has been deposited in the AMDCC website. With the information already available, the question of whether the plasma glucose levels across the duration of diabetes will be correlated with albuminuria and plasma creatinine levels (as markers of kidney function) as well as nerve conduction velocity and sensory loss (as markers of neuropathy) in aim 1. In aim 2, the data describing the quantitation of albuminuria and mesangial matrix will be correlated with nerve dysfunction. Data will be analyzed with the assistance of a tema of mentors that will include Dr. Sharma (for nephropathy), Dr. Nigel Calcutt for neuropathy, Dr. Tim Ravasi (for bioinformatic support) and Dr. Ronghui (Lily) Xu (for biostatistical support). Students will include one college student and two high school students who have some expertise basic biology research, bioinformatic analysis, and mouse models.


Progress Reports

Annual Reports

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Sharma, Kumar (2007)
2007Annual Report
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Sharma, Kumar (2008)
2008Annual Report
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Sharma, Kumar (2009)
2009Annual Report
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Sharma, Kumar (2010)
2010Annual Report
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Sharma, Kumar (2011)
2011Annual Report
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2016; Items: 1

 
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
27699244
Published

Year: 2015; Items: 2

 
Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease.
Börgeson E, Johnson AM, Lee YS, Till A, Syed GH, Ali-Shah ST, Guiry PJ, Dalli J, Colas RA, Serhan CN, Sharma K, Godson C
Cell Metabolism, 2015
26052006
Published
 
Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease.
You YH, Quach T, Saito R, Pham J, Sharma K
Journal of the American Society of Nephrology : JASN, 2015
26203118
Published

Year: 2014; Items: 5

 
Regulation of lipid accumulation by AMK-activated kinase in high fat diet-induced kidney injury.
Declèves AE, Zolkipli Z, Satriano J, Wang L, Nakayama T, Rogac M, Le TP, Nortier JL, Farquhar MG, Naviaux RK, Sharma K
Kidney international, 2014 (85), 611 - 623
24304883
Published
 
Adiponectin effects on the kidney.
Sweiss N, Sharma K
Best practice & research. Clinical endocrinology & metabolism, 2014 (28), 71 - 79
24417947
Published
 
Novel targets of antifibrotic and anti-inflammatory treatment in CKD.
Declèves AE, Sharma K
Nature reviews. Nephrology, 2014 (10), 257 - 267
24662433
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
 
AMP-activated protein kinase (AMPK) activation inhibits nuclear translocation of Smad4 in mesangial cells and diabetic kidneys.
Zhao J, Miyamoto S, You YH, Sharma K
American journal of physiology. Renal physiology, 2014, ajprenal.0
25428125
Published

Year: 2013; Items: 7

 
Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus.
Vallon V, Rose M, Gerasimova M, Satriano J, Platt KA, Koepsell H, Cunard R, Sharma K, Thomson SC, Rieg T
American journal of physiology. Renal physiology, 2013 (304), F156 - F167
23152292
Published
 
Role of Nox2 in diabetic kidney disease.
You YH, Okada S, Ly S, Jandeleit-Dahm K, Barit D, Namikoshi T, Sharma K
American journal of physiology. Renal physiology, 2013 (304), F840 - F848
23389458
Published
 
Obesity, immunomodulation and chronic kidney disease.
Börgeson E, Sharma K
Current opinion in pharmacology, 2013 (13), 618 - 624
23751262
Published
 
Autophagy and metabolic changes in obesity-related chronic kidney disease.
Satriano J, Sharma K
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013 (28 Suppl 4), iv29 - iv36
23901047
Published
 
Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease.
Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R, Pu M, Sharma S, You YH, Wang L, Diamond-Stanic M, Lindenmeyer MT, Forsblom C, Wu W, Ix JH, Ideker T, Kopp JB, Nigam SK, Cohen CD, Groop PH, Barshop BA, Natarajan L, Nyhan WL, Naviaux RK
Journal of the American Society of Nephrology : JASN, 2013 (24), 1901 - 1912
Submitted Externally
23949796
Published
 
AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function.
Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, Decleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W, Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, Sharma K
The Journal of clinical investigation, 2013 (123), 4888 - 4899
24135141
Published
 
Adipokines protecting CKD.
Miyamoto S, Sharma K
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013 (28 Suppl 4), iv15 - iv22
24179009
Published

Year: 2012; Items: 3

 
A role for the organic anion transporter OAT3 in renal creatinine secretion in mice.
Vallon V, Eraly SA, Rao SR, Gerasimova M, Rose M, Nagle M, Anzai N, Smith T, Sharma K, Nigam SK, Rieg T
American journal of physiology. Renal physiology, 2012 (302), F1293 - F1299
22338083
Published
 
Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model.
Østergaard JA, Bjerre M, RamachandraRao SP, Sharma K, Nyengaard JR, Hansen TK, Thiel S, Flyvbjerg A
Experimental diabetes research, 2012 (2012), 678381
22645604
Published
 
Sugar, sex, and TGF-ß in diabetic nephropathy.
Diamond-Stanic MK, You YH, Sharma K
Seminars in nephrology, 2012 (32), 261 - 268
22835457
Published

Year: 2011; Items: 4

 
Obesity related kidney disease.
Mathew AV, Okada S, Sharma K
Current diabetes reviews, 2011 (7), 41 - 49
21067508
Published
 
Invited Review- The Endoplasmic Reticulum Stress Response and Diabetic Kidney Disease.
Cunard R, Sharma K
American journal of physiology. Renal physiology, 2011
21345978
Published
 
Role of the USF1 transcription factor in diabetic kidney disease.
Sanchez AP, Zhao J, You Y, Declèves AE, Diamond-Stanic M, Sharma K
American journal of physiology. Renal physiology, 2011 (301), F271 - F279
21543418
Published
 
AMPK Mediates the Initiation of Kidney Disease Induced by a High-Fat Diet.
Declèves AE, Mathew AV, Cunard R, Sharma K
Journal of the American Society of Nephrology : JASN, 2011
21921143
Published

Year: 2010; Items: 7

 
Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy.
Rossini M, Naito T, Yang H, Freeman M, Donnert E, Ma LJ, Dunn SR, Sharma K, Fogo AB
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2010 (25), 1803 - 1810
20061322
Published
 
Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK.
Ix JH, Sharma K
Journal of the American Society of Nephrology : JASN, 2010 (21(3)), 406 - 412
20150538
Published
 
New pharmacological treatments for improving renal outcomes in diabetes.
Declèves AE, Sharma K
Nature reviews. Nephrology, 2010 (6), 371 - 380
20440278
Published
 
Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes.
Satriano J, Mansoury H, Deng A, Sharma K, Vallon V, Blantz RC, Thomson SC
American journal of physiology. Cell physiology, 2010 (299), C374 - C380
20505038
Published
 
Sodium-glucose transport: role in diabetes mellitus and potential clinical implications.
Vallon V, Sharma K
Current opinion in nephrology and hypertension, 2010 (19), 425 - 431
20539226
Published
 
TRB3 is stimulated in diabetic kidneys, regulated by the ER stress marker CHOP, and is a suppressor of podocyte MCP-1.
Morse E, Schroth J, You YH, Pizzo DP, Okada S, Ramachandrarao S, Vallon V, Sharma K, Cunard R
American journal of physiology. Renal physiology, 2010 (299), F965 - F972
20660016
Published
 
Role of reactive oxygen species in hyperadrenergic hypertension: biochemical, physiological, and pharmacological evidence from targeted ablation of the chromogranin a (Chga) gene.
Gayen JR, Zhang K, RamachandraRao SP, Mahata M, Chen Y, Kim HS, Naviaux RK, Sharma K, Mahata SK, O'Connor DT
Circulation. Cardiovascular genetics, 2010 (3), 414 - 425
20729505
Published

Year: 2009; Items: 5

 
Mechanisms of kidney fibrosis and the role of antifibrotic therapies
Leo Deelman and Kumar Sharma
Current opinion in nephrology and hypertension, 2009 (18), 85 - 90
19077695
Published
 
Transcription factors in the pathogenesis of diabetic nephropathy.
Sanchez AP, Sharma K
Expert reviews in molecular medicine, 2009 (11), e13
19397838
Published
 
The Link Between Obesity and Albuminuria: Adiponectin and Podocyte Dysfunction
Kumar Sharma
Kidney international, 2009 (76(2)), 145 - 148
19404275
Published
 
Pirfenidone is renoprotective in diabetic kidney disease.
RamachandraRao SP, Zhu Y, Ravasi T, McGowan TA, Toh I, Dunn SR, Okada S, Shaw MA, Sharma K
Journal of the American Society of Nephrology : JASN, 2009 (20(8)), 1765 - 1775
19578007
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: 1

 
Adiponectin regulates albuminuria and podocyte function in mice.
Kumar Sharma, M.D., Satish RamachandraRao, Ph.D., Gang Qiu, M.S., Hitomi Kataoka Usui, M.D., Yanqing Zhu, M.D., Stephen R. Dunn, B.S., Raogo Ouedraogo, Ph.D., Kelly Hough, Peter McCue, M.D., Lawrence Chan, M.D., Bonita Falkner, M.D., Barry J. Goldstein, M.D., Ph.D.
The Journal of clinical investigation, 2008 (118), 1645 - 1656
18431508
Published

Year: 2007; Items: 2

 
Regulation of transforming growth factor beta in diabetic nephropathy: implications for treatment.
Zhu Y, Usui HK, Sharma K
Seminars in nephrology, 2007 (27(2)), 153 - 160
17418684
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: 2005; Items: 2

 
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
 
Diabetic nephropathy: of mice and men.
Breyer MD, Böttinger E, Brosius FC, Coffman TM, Fogo A, Harris RC, Heilig CW, Sharma K
Advances in chronic kidney disease, 2005 (12(2)), 128 - 145
15822049
Published

Year: 2004; Items: 2

 
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
 
Utility of endogenous creatinine clearance as a measure of renal function in mice
Stephen Dunn, Zhonghua Qi, Erwin Bottinger, Metthew Breyer, Kumar Sharma
Kidney international, 2004 (65), 1959 - 1967
15086941
Published

Year: 2003; Items: 2

 
Diabetic kidney disease in the db/db mouse
Kumar Sharma, Peter McCue, and Stephen R. Dunn
American journal of physiology. Renal physiology, 2003 (284), F1138 - F1144
12736165
Published
 
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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Sharma, Kumar (2007)
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Sharma, Kumar (2009)
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No models found.