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PMID: 17884968 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Decorin deficiency enhances progressive nephropathy in diabetic mice.

The American journal of pathology ·Vol. 171 ·No. 5 ·2007-11-00 ·Pages 1441-50

Williams KJ, Qiu G, Usui HK, Dunn SR, McCue P, Bottinger E, Iozzo RV, Sharma K

Abstract

Decorin, a proteoglycan that inhibits active transforming growth factor-beta, is increased in diabetic nephropathy; however, its functional significance is unclear. In this study, we used low-dose streptozotocin to induce type 1 diabetes in wild-type (C57BL/6J Dcn(+/+)), Dcn(-/-), and Dcn(+/-) mice and studied the mice for up to 1 year of diabetes. Decorin gene dose had no effect on severity of diabetes; however, the Dcn(-/-) diabetic mice died significantly earlier than nondiabetic controls (57 versus 7.3% mortality). In contrast to wild-type diabetic mice, which failed to develop significant nephropathy, the Dcn(-/-) diabetic mice developed a significant increase in albuminuria and plasma creatinine and a concurrent decrease in circulating adiponectin levels. Interestingly, adiponectin levels at 6 months of diabetes were predictive of mortality in diabetic mice. Dcn(-/-) diabetic mice exhibited advanced glomerular lesions, including diffuse mesangial matrix accumulation and fibrin cap formation. By immunohistochemistry, Dcn(-/-) diabetic mice exhibited significant increases in glomerular transforming growth factor-beta, type I collagen, macrophage infiltration, and Nox4. We conclude that decorin is a natural protective factor against diabetic nephropathy and that the Dcn(-/-) diabetic mouse is a useful new model of progressive diabetic nephropathy.

MeSH Terms
Animals Collagen Type I/metabolism Decorin Diabetes Mellitus, Experimental/metabolism,pathology,physiopathology Diabetes Mellitus, Type 1/metabolism,pathology,physiopathology Diabetic Nephropathies/metabolism,pathology,physiopathology Extracellular Matrix Proteins/genetics,physiology Kidney Glomerulus/immunology,metabolism,pathology Macrophages/immunology Male Mice Mice, Inbred C57BL Mice, Knockout NADPH Oxidase 4 NADPH Oxidases/metabolism Proteoglycans/genetics,physiology Streptozocin Transforming Growth Factor beta/metabolism
Chemicals
Collagen Type I Dcn protein, mouse Decorin Extracellular Matrix Proteins Proteoglycans Transforming Growth Factor beta Streptozocin NADPH Oxidase 4 NADPH Oxidases Nox4 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Williams Kevin Jon
Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Qiu Gang
Usui Hitomi Katoaka
Dunn Stephen R
McCue Peter
Bottinger Erwin
Iozzo Renato V
Sharma Kumar
References (49)
49 references, click to expand
  1. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility.
    J Cell Biol. 1997 Feb 10;136(3):729-43 PMID: 9024701
  2. Extracellular matrix/growth factor interactions.
    Cold Spring Harb Symp Quant Biol. 1992;57:309-15 PMID: 1339667
  3. Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation.
    Am J Physiol. 1997 Apr;272(4 Pt 2):F515-20 PMID: 9140053
  4. The family of the small leucine-rich proteoglycans: key regulators of matrix assembly and cellular growth.
    Crit Rev Biochem Mol Biol. 1997;32(2):141-74 PMID: 9145286
  5. Increased decorin mRNA in diabetic mouse kidney and in mesangial and tubular cells cultured in high glucose.
    Am J Physiol. 1998 Nov;275(5 Pt 2):F827-32 PMID: 9815141
  6. Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.
    J Biol Chem. 1999 Feb 26;274(9):5830-4 PMID: 10026205
  7. The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins.
    J Biol Chem. 1999 Jul 2;274(27):18843-6 PMID: 10383378
  8. Development of late-stage diabetic nephropathy in OVE26 diabetic mice.
    Diabetes. 2004 Dec;53(12):3248-57 PMID: 15561957
  9. Mouse models of diabetic nephropathy.
    J Am Soc Nephrol. 2005 Jan;16(1):27-45 PMID: 15563560
  10. The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study.
    Diabetologia. 2005 Jan;48(1):41-8 PMID: 15616802
  11. Low plasma adiponectin levels predict progression of coronary artery calcification.
    Circulation. 2005 Feb 15;111(6):747-53 PMID: 15699257
  12. Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study.
    J Am Soc Nephrol. 2005 Apr;16(4):1091-8 PMID: 15743998
  13. Can murine diabetic nephropathy be separated from superimposed acute renal failure?
    Kidney Int. 2005 Jul;68(1):391-8 PMID: 15954931
  14. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial.
    J Am Soc Nephrol. 2005 Jul;16(7):2170-9 PMID: 15930097
  15. Characterization of susceptibility of inbred mouse strains to diabetic nephropathy.
    Diabetes. 2005 Sep;54(9):2628-37 PMID: 16123351
  16. Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.
    Am J Physiol Renal Physiol. 2005 Oct;289(4):F816-25 PMID: 16159901
  17. Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension.
    Am J Cardiol. 2005 Oct 1;96(7):946-51 PMID: 16188522
  18. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney.
    J Biol Chem. 2005 Nov 25;280(47):39616-26 PMID: 16135519
  19. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy.
    Diabetes. 2006 Jan;55(1):225-33 PMID: 16380497
  20. Adiponectin is inversely associated with renal function in type 1 diabetic patients.
    J Clin Endocrinol Metab. 2006 Jan;91(1):129-35 PMID: 16219717
  21. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells.
    Am J Physiol Lung Cell Mol Physiol. 2006 Apr;290(4):L661-L673 PMID: 16227320
  22. Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice.
    Atherosclerosis. 2006 Jul;187(1):31-9 PMID: 16183063
  23. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice.
    J Am Soc Nephrol. 2006 Oct;17(10):2664-9 PMID: 16971655
  24. Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8015-20 PMID: 10859350
  25. The decorin high glucose response element and mechanism of its activation in human mesangial cells.
    J Am Soc Nephrol. 2000 Sep;11(9):1607-19 PMID: 10966485
  26. An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.
    Anal Biochem. 1994 Feb 1;216(2):276-84 PMID: 8179182
  27. Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator.
    Diabetes. 1995 Oct;44(10):1139-46 PMID: 7556948
  28. Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene.
    Diabetes. 2006 Nov;55(11):3166-74 PMID: 17065357
  29. Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy.
    J Am Soc Nephrol. 2007 Feb;18(2):539-50 PMID: 17202420
  30. Small proteoglycans in human diabetic nephropathy: discrepancy between glomerular expression and protein accumulation of decorin, biglycan, lumican, and fibromodulin.
    FASEB J. 2001 Mar;15(3):559-61 PMID: 11259366
  31. Diabetic nephropathy.
    Clin Lab Med. 2001 Mar;21(1):111-46 PMID: 11321931
  32. Glomerular cell number in normal subjects and in type 1 diabetic patients.
    Kidney Int. 2001 Jun;59(6):2104-13 PMID: 11380812
  33. Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis.
    Curr Opin Lipidol. 2001 Oct;12(5):477-87 PMID: 11561166
  34. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.
    J Am Soc Nephrol. 2002 Jan;13(1):134-41 PMID: 11752030
  35. Absence of decorin adversely influences tubulointerstitial fibrosis of the obstructed kidney by enhanced apoptosis and increased inflammatory reaction.
    Am J Pathol. 2002 Mar;160(3):1181-91 PMID: 11891213
  36. A new method for large scale isolation of kidney glomeruli from mice.
    Am J Pathol. 2002 Sep;161(3):799-805 PMID: 12213707
  37. Diabetic kidney disease in the db/db mouse.
    Am J Physiol Renal Physiol. 2003 Jun;284(6):F1138-44 PMID: 12736165
  38. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy.
    J Am Soc Nephrol. 2003 Aug;14(8 Suppl 3):S221-6 PMID: 12874435
  39. Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes.
    Diabetes. 2003 Oct;52(10):2586-93 PMID: 14514644
  40. Increased expression of NAD(P)H oxidase subunits, NOX4 and p22phox, in the kidney of streptozotocin-induced diabetic rats and its reversibity by interventive insulin treatment.
    Diabetologia. 2003 Oct;46(10):1428-37 PMID: 13680125
  41. Molecular profiling of diabetic mouse kidney reveals novel genes linked to glomerular disease.
    Diabetes. 2004 Mar;53(3):784-94 PMID: 14988265
  42. Utility of endogenous creatinine clearance as a measure of renal function in mice.
    Kidney Int. 2004 May;65(5):1959-67 PMID: 15086941
  43. Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes.
    J Clin Endocrinol Metab. 2004 Aug;89(8):4010-7 PMID: 15292342
  44. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
    N Engl J Med. 2004 Sep 23;351(13):1296-305 PMID: 15385656
  45. Structural-functional relationships in diabetic nephropathy.
    J Clin Invest. 1984 Oct;74(4):1143-55 PMID: 6480821
  46. High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-beta.
    Kidney Int. 1992 Sep;42(3):647-56 PMID: 1357223
  47. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.
    Nature. 1992 Nov 26;360(6402):361-4 PMID: 1280332
  48. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy.
    Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1814-8 PMID: 7680480
  49. Increased renal production of transforming growth factor-beta1 in patients with type II diabetes.
    Diabetes. 1997 May;46(5):854-9 PMID: 9133555
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2007.070079
Published
2007-11-00
Epub
2007-00-20
Pages
1441-50
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC2043506
Subset
IM
Grants
NHLBI NIH HHS · P50 HL056984 · United States
NIDDK NIH HHS · R01 DK056077 · United States
NIDDK NIH HHS · U01 DK060995 · United States
NIDDK NIH HHS · U01 DK60995 · United States
NCI NIH HHS · R01 CA039481 · United States
NIDDK NIH HHS · R01 DK073960 · United States
NCI NIH HHS · CA 39481 · United States
NHLBI NIH HHS · HL56984 · United States
NIDDK NIH HHS · R01 DK060043 · United States
NIDDK NIH HHS · DK053867 · United States
NIDDK NIH HHS · R01 DK053867 · United States
External Links
PubMed source DOI: 10.2353/ajpath.2007.070079 PMC Full Text View journal details
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