TY - JOUR A1 - Gutwein, Paul A1 - Abdel-Bakky, Mohamed Sadek A1 - Doberstein, Kai A1 - Schramme, Anja A1 - Beckmann, Janet A1 - Schäfer, Liliana A1 - Amann, Kerstin Ute A1 - Doller, Anke A1 - Kämpfer-Kolb, Nicole A1 - Abdel-Aziz, Abdel-Aziz H. A1 - El Sayed, El Sayed M. A1 - Pfeilschifter, Josef T1 - CXCL16 and oxLDL are induced in the onset of diabetic nephropathy T2 - Journal of cellular and molecular medicine N2 - 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. KW - CXCL16 KW - diabetic nephropathy KW - ADAM10 KW - podocytes KW - primary tubular cells Y1 - 2009 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28763 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-287633 UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516529/ SN - 1582-4934 SN - 1582-1838 N1 - © 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. VL - 13 IS - 9b SP - 3809 EP - 3825 PB - Wiley-Blackwell CY - Hoboken, NJ ER -