Search: id:"swepub:oai:DiVA.org:uu-239742" >
Role of Heparanase-...
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Goldberg, Rachel
(author)
Role of Heparanase-Driven Inflammatory Cascade in Pathogenesis of Diabetic Nephropathy
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2014-11-13
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American Diabetes Association,2014
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-239742
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-239742URI
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https://doi.org/10.2337/db14-0001DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Renal involvement is a major medical concern in the diabetic population, and with the global epidemic of diabetes, diabetic nephropathy (DN) became the leading cause of end-stage renal failure in the Western world. Heparanase (the only known mammalian endoglycosidase that cleaves heparan sulfate) is essentially involved in DN pathogenesis. Nevertheless, the exact mode of heparanase action in sustaining the pathology of DN remains unclear. Here we describe a previously unrecognized combinatorial circuit of heparanase-driven molecular events promoting chronic inflammation and renal injury in individuals with DN. These events are fueled by heterotypic interactions among glomerular, tubular, and immune cell compartments, as well as diabetic milieu (DM) components. We found that under diabetic conditions latent heparanase, overexpressed by glomerular cells and posttranslationally activated by cathepsin L of tubular origin, sustains continuous activation of kidney-damaging macrophages by DM components, thus creating chronic inflammatory conditions and fostering macrophage-mediated renal injury. Elucidation of the mechanism underlying the enzyme action in diabetic kidney damage is critically important for the proper design and future implementation of heparanase-targeting therapeutic interventions (which are currently under intensive development and clinical testing) in individuals with DN and perhaps other complications of diabetes.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Rubinstein, Ariel M.
(author)
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Gil, Natali
(author)
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Hermano, Esther
(author)
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Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)jinpili
(author)
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van der Vlag, Johan
(author)
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Atzmon, Ruth
(author)
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Meirovitz, Amichay
(author)
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Elkin, Michael
(author)
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Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi
(creator_code:org_t)
Related titles
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In:Diabetes: American Diabetes Association63:12, s. 4302-43130012-17971939-327X
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