CXCL16 and oxLDL are induced in the onset of diabetic nephropathy

Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune compl
Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune complexes were found in patients with DN. In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. In contrast, in primary tubular cells CD36 was mainly involved in the uptake of oxLDL. We further demonstrate that oxLDL down-regulated α3-integrin expression and increased the production of fibronectin in human podocytes. In addition, oxLDL uptake induced the production of reactive oxygen species (ROS) in human podocytes. Inhibition of oxLDL uptake by CXCL16 blocking antibodies abrogated the fibronectin and ROS production and restored α3 integrin expression in human podocytes. Furthermore we present evidence that hyperglycaemic conditions increased CXCL16 and reduced ADAM10 expression in podocytes. Importantly, in streptozotocin-induced diabetic mice an early induction of CXCL16 was accompanied by higher levels of oxLDL. Finally immunofluorescence analysis in biopsies of patients with DN revealed increased glomerular CXCL16 expression, which was paralleled by high levels of oxLDL. In summary, regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN.
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Metadaten
Author:Paul Gutwein, Mohamed Sadek Abdel-Bakky, Kai Doberstein, Anja Schramme, Janet Beckmann, Liliana Schäfer, Kerstin Ute Amann, Anke Doller, Nicole Kämpfer-Kolb, Abdel-Aziz H. Abdel-Aziz, El Sayed M. El Sayed, Josef Martin Pfeilschifter
URN:urn:nbn:de:hebis:30:3-287633
URL:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516529/
DOI:http://dx.doi.org/10.1111/j.1582-4934.2009.00761.x
ISSN:1582-4934
ISSN:1582-1838
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=19426159
Parent Title (English):Journal of cellular and molecular medicine
Publisher:Wiley-Blackwell
Place of publication:Hoboken, NJ
Document Type:Article
Language:English
Date of Publication (online):2009/05/01
Date of first Publication:2009/05/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/08
Tag:ADAM10; CXCL16; diabetic nephropathy; podocytes; primary tubular cells
Volume:13
Issue:9b
Pagenumber:17
First Page:3809
Last Page:3825
Note:
© 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
HeBIS PPN:328054674
Institutes:Medizin
Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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