Heparanase is involved in the pathogenesis of proteinuria as a result of glomerulonephritis
- PMID: 14694159
- DOI: 10.1097/01.asn.0000103229.25389.40
Heparanase is involved in the pathogenesis of proteinuria as a result of glomerulonephritis
Abstract
The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by selectively degrading the negatively charged side chains of heparan sulfate proteoglycans within the glomerular basement membrane. A loss of negatively charged heparan sulfate proteoglycans may result in alteration of the permselective properties of the glomerular basement membrane, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. In this study, therefore, the role of heparanase in passive Heymann nephritis (PHN) was examined. Normal glomeruli showed low-level heparanase expression as determined by immunohistochemistry and Western blot analysis. Days 5, 14, and 28 of PHN were associated with an increase in endothelial and glomerular epithelial cell heparanase. Reverse transcription-PCR confirmed a significant increase in mRNA at day 21 of disease (P < 0.0004). Furthermore, urinary and glomerular heparanase activities were significantly increased at days 5 and 21 of disease, respectively. Western blot analysis of isolated glomeruli separated into membrane- and cytosol-enriched protein fractions showed that the active 58-kD heparanase species was increased but restricted to the cytosol of diseased glomeruli at day 21. The inactive 65-kD precursor, however, was found in membrane and cytosol-diseased fractions, suggesting cell membrane processing. Complement depletion prevented glomerular heparanase expression; in addition, administration of a polyclonal anti-heparanase antibody significantly reduced urinary protein excretion at day 5 of disease to 62 +/- 11 mg/d compared with 203 +/- 43 and 159 +/- 18 mg/d in the normal rabbit serum- and normal saline-treated experimental groups, respectively (P < 0.002). Proteinuria was reduced in the absence of any altered glomerular C5b-9 activity, sheep IgG deposition, or rat anti-sheep antibody titers. These data suggest that heparanase contributes to the pathogenesis of proteinuria in PHN.
Similar articles
-
A synthetic heparanase inhibitor reduces proteinuria in passive Heymann nephritis.J Am Soc Nephrol. 2004 Nov;15(11):2882-92. doi: 10.1097/01.ASN.0000142426.55612.6D. J Am Soc Nephrol. 2004. PMID: 15504941
-
Heparanase inhibition reduces proteinuria in a model of accelerated anti-glomerular basement membrane antibody disease.Nephrology (Carlton). 2005 Apr;10(2):167-73. doi: 10.1111/j.1440-1797.2005.00388.x. Nephrology (Carlton). 2005. PMID: 15877677
-
Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis.Virchows Arch. 2001 Feb;438(2):136-45. doi: 10.1007/s004280000295. Virchows Arch. 2001. PMID: 11253115
-
The role of heparanase in diseases of the glomeruli.Arch Immunol Ther Exp (Warsz). 2010 Feb;58(1):45-56. doi: 10.1007/s00005-009-0061-6. Epub 2010 Jan 5. Arch Immunol Ther Exp (Warsz). 2010. PMID: 20049646 Review.
-
Heparanase in glomerular diseases.Kidney Int. 2007 Sep;72(5):543-8. doi: 10.1038/sj.ki.5002337. Epub 2007 May 23. Kidney Int. 2007. PMID: 17519955 Review.
Cited by
-
Early diabetic kidney disease: Focus on the glycocalyx.World J Diabetes. 2023 May 15;14(5):460-480. doi: 10.4239/wjd.v14.i5.460. World J Diabetes. 2023. PMID: 37273258 Free PMC article. Review.
-
Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury.Int J Mol Sci. 2022 Oct 21;23(20):12691. doi: 10.3390/ijms232012691. Int J Mol Sci. 2022. PMID: 36293542 Free PMC article.
-
Prevention of Triglyceridemia by (Non-)Anticoagulant Heparin(oids) Does Not Preclude Transplant Vasculopathy and Glomerulosclerosis.Front Cell Dev Biol. 2022 Mar 7;10:798088. doi: 10.3389/fcell.2022.798088. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 35345850 Free PMC article.
-
Heparanase in Acute Kidney Injury.Adv Exp Med Biol. 2020;1221:685-702. doi: 10.1007/978-3-030-34521-1_28. Adv Exp Med Biol. 2020. PMID: 32274732 Free PMC article. Review.
-
Alternative Pathway Is Essential for Glomerular Complement Activation and Proteinuria in a Mouse Model of Membranous Nephropathy.Front Immunol. 2018 Jun 22;9:1433. doi: 10.3389/fimmu.2018.01433. eCollection 2018. Front Immunol. 2018. PMID: 29988342 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources