Increased expression of heparanase in puromycin aminonucleoside nephrosis

Levidiotis, Vicki; Kanellis, John; Ierino, Frank; Power, David A.

doi:10.1046/j.1523-1755.2001.00934.x

Cited by 62 publications

(71 citation statements)

References 27 publications

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“…Our study demonstrates that heparanase expression is increased in AN and correlated with the loss of HS in the GBM, suggesting that heparanase may play an important role in HS reduction. The increased expression of heparanase in AN is in line with the findings in puromycin aminonucleoside nephrosis, passive Heymann nephritis, and anti-GBM nephritis (15)(16)(17)(18). The loss of glomerular HS also is in accordance with previous studies in proteinuric renal disease (7)(8)(9).…”

Section: Discussionsupporting

confidence: 90%

“…A recent study in patients with diabetic nephropathy suggested that loss of HS in the GBM is attributable to accelerated HS degradation by increased heparanase expression (14). Studies in experimental renal diseases (passive Heymann nephritis, puromycin aminonucleoside nephrosis, and anti-GBM nephritis) suggest that heparanase also may be involved in nondiabetic proteinuric disease (15)(16)(17)(18).…”

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confidence: 99%

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Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Kramer¹,

Hoven²,

Rops³

et al. 2006

Journal of the American Society of Nephrology

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Heparan sulfate (HS) in the glomerular basement membrane (GBM) is important for regulation of the charge-dependent permeability. Heparanase has been implicated in HS degradation in several proteinuric diseases. This study analyzed the role of heparanase in HS degradation in Adriamycin nephropathy (AN), a model of chronic proteinuria-induced renal damage. Expression of heparanase, HS, and the core protein of agrin (to which HS is attached) was determined on kidney sections from rats with AN in different experiments. First, expression was examined in a model of unilateral AN in a time-course study at 6-wk intervals until week 30. Second, rats were treated with the hydroxyl radical scavenger dimethylthiourea (DMTU) during bilateral AN induction. Finally, 6 wk after AN induction, rats were treated with angiotensin II receptor type 1 antagonist (AT1A) or vehicle for 2 wk. Heparanase expression was increased in glomeruli of rats with AN, which correlated with HS reduction at all time points and in all experiments. Treatment with DMTU prevented the increased heparanase expression, the loss of GBM HS, and reduced albuminuria. Finally, treatment of established proteinuria with AT1A significantly reduced heparanase expression and restored glomerular HS. In conclusion, an association between heparanase expression and reduction of glomerular HS in AN was observed. The effects of DMTU suggest a role for reactive oxygen species in upregulation of heparanase. Antiproteinuric treatment by AT1A decreased heparanase expression and restored HS expression. These results suggest involvement of radicals and angiotensin II in the modulation of GBM permeability through HS and heparanase expression.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Kramer¹,

Hoven²,

Rops³

et al. 2006

Journal of the American Society of Nephrology

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“…In the past 5 years, upregulation of glomerular heparanase gene expression has been shown in numerous clinical or experimental nephropathies such as puromycin aminonucleoside nephrosis [30], passive Heymann nephritis [31], anti-GBM nephritis [32], adriamycin nephropathy [33], streptozotocin-induced diabetic nephropathy [11], minimal change nephrotic syndrome, and membranous glomerulopathy [34]. The molecular mechanisms that regulate heparanase gene expression and activity still have to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

et al. 2007

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Aims/hypothesis Recent studies suggest that loss of heparan sulphate in the glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due to the increased production of heparanase, a heparan sulphate-degrading endoglycosidase. Our present study addresses whether heparan sulphate with different modifications is differentially reduced in the GBM and whether heparanase selectively cleaves heparan sulphate with different domain specificities. Methods The heparan sulphate content of renal biopsies (14 diabetic nephropathy, five normal) were analysed by immunofluorescence staining with four anti-heparan sulphate antibodies: JM403, a monoclonal antibody (mAb) recognising N-unsubstituted glucosamine residues; two phage displayderived single chain antibodies HS4C3 and EW3D10, defining sulphated heparan sulphate domains; and anti-K5 antibody, an mAb recognising unmodified heparan sulphate domains. Results We found that modified heparan sulphate domains (JM403, HS4C3 and EW3D10), but not unmodified domains (anti-K5) and agrin core protein were reduced in the GBM of kidneys from patients with diabetic nephropathy, compared with controls. Glomerular heparanase levels were increased in diabetic nephropathy kidneys and inversely correlated with the amounts of modified heparan sulphate domains. Increased heparanase production and loss of JM403 staining in the GBM Diabetologia (2008) 51:372-382

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“…Heparanase up-regulation has been documented in a variety of human tumors correlating, in some cases, with increased vascular density and poor postoperative survival (14 -17). Heparanase overexpression has also been noted in several other pathologies such as cirrhosis (18), nephrosis (19), and diabetes (20). In addition to its intimate involvement in the egress of cells from the blood stream, heparanase activity may release a multitude of HS-bound, extracellular matrix-resident growth factors, cytokines, chemokines, and enzymes that might profoundly affect cell and tissue function (1,21).…”

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confidence: 99%

Heparanase Uptake Is Mediated by Cell Membrane Heparan Sulfate Proteoglycans

Gingis-Velitski¹,

Zetser²,

Kaplan³

et al. 2004

Journal of Biological Chemistry

162

211

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Heparanase is a mammalian endoglycosidase that degrades heparan sulfate (HS) at specific intrachain sites, an activity that is strongly implicated in cell dissemination associated with metastasis and inflammation. In addition to its structural role in extracellular matrix assembly and integrity, HS sequesters a multitude of polypeptides that reside in the extracellular matrix as a reservoir. A variety of growth factors, cytokines, chemokines, and enzymes can be released by heparanase activity and profoundly affect cell and tissue function. Thus, heparanase bioavailability, accessibility, and activity should be kept tightly regulated. We provide evidence that HS is not only a substrate for, but also a regulator of, heparanase. Addition of heparin or xylosides to cell cultures resulted in a pronounced accumulation of, heparanase in the culture medium, whereas sodium chlorate had no such effect. Moreover, cellular uptake of heparanase was markedly reduced in HS-deficient CHO-745 mutant cells, heparan sulfate proteoglycan-deficient HT-29 colon cancer cells, and heparinasetreated cells. We also studied the heparanase biosynthetic route and found that the half-life of the active enzyme is ϳ30 h. This and previous localization studies suggest that heparanase resides in the endosomal/lysosomal compartment for a relatively long period of time and is likely to play a role in the normal turnover of HS. Co-localization studies and cell fractionation following heparanase addition have identified syndecan family members as candidate molecules responsible for heparanase uptake, providing an efficient mechanism that limits extracellular accumulation and function of heparanase.

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Increased expression of heparanase in puromycin aminonucleoside nephrosis

Cited by 62 publications

References 27 publications

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

Heparanase Uptake Is Mediated by Cell Membrane Heparan Sulfate Proteoglycans

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