HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fornoni, A. Articles by Striker, G. E. Search for Related Content PubMed PubMed Citation Articles by Fornoni, A. Articles by Striker, G. E. Social Bookmarking                What's this?

Reversibility of Glucose-Induced Changes in Mesangial Cell Extracellular Matrix Depends on the Genetic Background

From the University of Miami School of Medicine, Vascular Biology Institute, Miami, Florida

Adequate glycemic control protects most patients with diabetes from nephropathy, but a substantial fraction of patients develop progressive disease despite lowering glycemia. We isolated mesangial cells (MC) from the glomeruli of mouse strains that model these two outcomes in patients with diabetes, namely those that have the propensity (ROP) or resistance (B6) to develop progressive diabetic nephropathy. We determined the nature and reversibility of changes in selected extracellular matrix-related molecules after chronic exposure to elevated glucose concentration. MC were exposed to 25 mmol/l glucose for 5 weeks followed by 6 mmol/l glucose and 19 mmol/l mannitol for an additional 5 weeks. Matrix metalloproteinase-2 (MMP-2) and transforming growth factor-ß₁ (TGF-ß₁) levels increased in B6 MC exposed to 25 mmol/l glucose but returned to baseline levels when the glucose concentration was reduced to 6 mmol/l. MMP-2 and TGF-ß₁ were higher in ROP MC at baseline and increased in response to 25 mmol/l glucose, but remained elevated when glucose concentration was reduced. Type I collagen expression and accumulation increased in a reversible manner in B6 MC exposed to 25 mmol/l glucose. However, type I collagen expression was higher in ROP MC at baseline and remained unaffected by changes in glucose concentration. Thus, 25 mmol/l glucose induced reversible changes in MMP-2, TGF-ß₁, and type I collagen in MC of sclerosis-resistant mice but not in MC from sclerosis-prone mice. Therefore, progressive diabetic nephropathy may be secondary to stable alterations in the phenotype of MC as a result of the interplay between the genetic background and elevated glucose concentrations.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. Fornoni, S. A. Rosenzweig, O. Lenz, A. Rivera, G. E. Striker, and S. J. Elliot Low Insulin-Like Growth Factor Binding Protein-2 Expression Is Responsible for Increased Insulin Receptor Substrate-1 Phosphorylation in Mesangial Cells from Mice Susceptible to Glomerulosclerosis Endocrinology, July 1, 2006; 147(7): 3547 - 3554. [Abstract] [Full Text] [PDF]

				A. Inada, K. Nagai, H. Arai, J.-i. Miyazaki, K. Nomura, H. Kanamori, S. Toyokuni, Y. Yamada, S. Bonner-Weir, G. C. Weir, et al. Establishment of a Diabetic Mouse Model with Progressive Diabetic Nephropathy Am. J. Pathol., August 1, 2005; 167(2): 327 - 336. [Abstract] [Full Text] [PDF]

				N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]

				F. Zheng, Q.-L. Cheng, A.-R. Plati, S. Q. Ye, M. Berho, A. Banerjee, M. Potier, E. A. Jaimes, H. Yu, Y.-F. Guan, et al. The Glomerulosclerosis of Aging in Females: Contribution of the Proinflammatory Mesangial Cell Phenotype to Macrophage Infiltration Am. J. Pathol., November 1, 2004; 165(5): 1789 - 1798. [Abstract] [Full Text] [PDF]

				C. Dai, J. Yang, S. Bastacky, J. Xia, Y. Li, and Y. Liu Intravenous Administration of Hepatocyte Growth Factor Gene Ameliorates Diabetic Nephropathy in Mice J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2637 - 2647. [Abstract] [Full Text] [PDF]

				F. Zheng, F. Cornacchia, I. Schulman, A. Banerjee, Q.-l. Cheng, M. Potier, A. R. Plati, M. Berho, S. J. Elliot, J. Li, et al. Development of Albuminuria and Glomerular Lesions in Normoglycemic B6 Recipients of db/db Mice Bone Marrow: The Role of Mesangial Cell Progenitors Diabetes, September 1, 2004; 53(9): 2420 - 2427. [Abstract] [Full Text] [PDF]

				A. Fornoni, O. Lenz, L. J. Striker, and G. E. Striker Glucose Induces Clonal Selection and Reversible Dinucleotide Repeat Expansion in Mesangial Cells Isolated from Glomerulosclerosis-Prone Mice Diabetes, October 1, 2003; 52(10): 2594 - 2602. [Abstract] [Full Text] [PDF]

				F. Zheng, A. R. Plati, M. Potier, Y. Schulman, M. Berho, A. Banerjee, B. Leclercq, A. Zisman, L. J. Striker, and G. E. Striker Resistance to Glomerulosclerosis in B6 Mice Disappears after Menopause Am. J. Pathol., April 1, 2003; 162(4): 1339 - 1348. [Abstract] [Full Text] [PDF]

				A. Fornoni, Y. Wang, O. Lenz, L. J. Striker, and G. E. Striker Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice J. Am. Soc. Nephrol., August 1, 2002; 13(8): 2068 - 2076. [Abstract] [Full Text] [PDF]