The kidney disease of diabetes mellitus (KDDM): A cell and molecular biology approach

Striker, Gary E.; Peten, Emmanuel P.; Pesce, Carlo; Schmidt, K.J.; Yang, Chih‐Wei; Elliot, Sharon J.; Striker, Liliane J.; Carome, Michael A.

doi:10.1002/dmr.5610090105

Cited by 41 publications

(24 citation statements)

References 73 publications

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“…Diabetes mellitus is a common metabolic disorder in which the hyperglycemic state seems to adversely affect the homeostasis of various organ systems, including the kidney (1,2). The pathologic changes of the kidney are characterized by biochemical alterations of the extracellular matrix (ECM) 1 macromolecules; the latter are believed to regulate morphogenesis of different organ systems (3,4).…”

Section: Introductionmentioning

confidence: 99%

D-glucose-induced dysmorphogenesis of embryonic kidney.

Kanwar¹,

Liu²,

Kumar³

et al. 1996

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 99%

D-glucose-induced dysmorphogenesis of embryonic kidney.

Kanwar¹,

Liu²,

Kumar³

et al. 1996

J. Clin. Invest.

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“…MC have been postulated to be major contributors to glomerulosclerotic lesions (19) and have been demonstrated to express MMP-9 in certain species and experimental conditions (20 -22). The behavior of MC in vitro might be different from that in vivo, and behavior is influenced by the substrate and cell culture conditions (23).…”

mentioning

confidence: 99%

Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice

Fornoni

Wang

Lenz

et al. 2002

Journal of the American Society of Nephrology

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Abstract. The genetic background plays an important role in the development of progressive glomerulosclerosis. However, no marker is available for the reliable prediction of genetic susceptibility to glomerulosclerosis. Because matrix metalloproteinase-9 (MMP-9) levels are decreased in models of glomerulosclerosis and MMP-9 promoter polymorphism has been observed among patients with diabetic nephropathy, MMP-9 could be one such marker. The object of this study was to determine whether MMP-9 promoter polymorphism was associated with altered MMP-9 expression in mesangial cells (MC) from two mouse strains, i.e., ROP (glomerulosclerosis prone) and B6SJL (glomerulosclerosis resistant). ROP MC expressed 12-fold less MMP-9 mRNA. The MMP-9 promoter in ROP MC contained fewer d(CA) repeats, which was associated with lower MMP-9 expression and activity. Phorbol-12-myristate-13-acetate (3 to 60 ng/ml) increased MMP-9 expression in both MC types (3-to 4.5-fold), but the level in ROP MC never reached that in B6SLJ MC. Although reciprocal transfection of ROP and B6SJL MMP-9 promoter constructs into B6SJL and ROP cells revealed that the promoters were functional in both cell types, the B6SJL promoter was less responsive to phorbol-12-myristate-13-acetate stimulation when transfected into ROP MC, suggesting a role for other factors. In conclusion, the MMP-9 promoter exhibits a decreased number of d(CA) repeats in the sclerosis-prone strain. Because fewer d(CA) repeats associated with decreased MMP-9 expression in MC, it might be a genetic marker for glomerulosclerosis.

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“…A subgroup ofpatients with diabetes mellitus may experience glomerulosclerosis as a result of mesangial expansion, a process that can progress to renal failure (1). The proximal cause of this process differs from that of the nephrosclerosis of aging, which more likely reflects the effects of vascular lesions with atrophic glomeruli and ischemia (2).…”

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confidence: 99%

Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats.

Vlassara¹,

Striker

Teichberg

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

429

276

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High levels of tissue advanced glycation end products (AGEs) that result from the spontaneous modification of proteins by glucose occur In diabetes and aging. To address the potential pathogenic role of AGEs in the glomerulosclerosis of diabetes or nephrosclerosls of aging, doses of AGE-modified rat albumin (25 mg per kg per day, i.v.) sufficient to elevate circulating AGE levels to the range of diabetic serum were admired daily to healthy rats alone or in combination with the AGE inhibitor ae. After 5 months, the AGE content of renal tissues in AGE-treated rats rose to 50% above controls (P < 0.025), whereas serum contained 2.8-fold greater AGE levels (P < 0.025). Light and electron microscopy of kidneys from AGE-treated rats revealed a more than 50% increase in glomerular volume compared to controls (P < 0.001), I t periodic add/Schiff reagent-positive deposits, basement membrane widening, and mesanga extraceflular matrix increase and indicated significant glomerulosclerosis compared to untreated (P < 0.002) or albumin-treated controls (P < 0.002). These changes were associated with si nt loss of protein (P < 0.005) and albumin (P < 0.002) in the urine of AGE-treated rats compared to controls. Cotreatment with aminoguanidine markedly limited both the structural and fuctional defects. These in vivo data demonstrate that AGEs influence glomerular structure and function in a manner leading to glomerulosclerosis. (8), while in normal SJL mice AGEs enhance the expression of alIV collagen and laminin B1 mRNAs within the glomerulus (9). However, the long-term impact of cumulative AGE deposition on the structure and function of the kidney has remained obscure.In this report, we present evidence indicating that prolonged in vivo exposure of normal renal tissues to AGEmodified homologous serum albumin induces marked renal lesions and that certain aspects ofthis pathology are inhibited by the coadministration of aminoguanidine. METHODSPreparation of Advanced Glycation Products. Rat serum albumin (RSA) (Sigma) was passed over an Affi-Gel Blue column (Bio-Rad), a heparin-Sepharose CL-6B column (Pharmacia), and an endotoxin-binding affinity column (Detoxigel, Pierce) to remove possible contaminants (8, 9). RSA modified by AGEs was prepared as described (8,9). AGE levels were measured by an AGE-specific ELISA (10) (AGE-rat albumin, 62 AGE units/mg of protein; unmodified rat albumin, 1.2 units/mg). Each reagent contained endotoxin (E-Toxate, Sigma) at <0.2 ng/ml. Animal Studies. Male Sprague-Dawley rats (150 g) aged 3 months (n = 50) (Charles River Breeding Laboratories) were used in these studies, which were conducted in accordance with The Picower Institute Laboratory Animal Center guidelines. After a 2-week adaptation period, rats were given tail vein injections with AGE-modified or native RSA (25 mg per kg per day) or with AGE-RSA followed by infusions of aminoguanidine hydrochloride (100 mg per kg per day, i.v.) for 5 months. Serum samples were collected at the end ofthe treatment period from all groups for seru...

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The kidney disease of diabetes mellitus (KDDM): A cell and molecular biology approach

Cited by 41 publications

References 73 publications

D-glucose-induced dysmorphogenesis of embryonic kidney.

D-glucose-induced dysmorphogenesis of embryonic kidney.

Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice

Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats.

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