Open AccessCXCL16 and oxLDL are induced in the onset of diabetic nephropathy
Author(s) -
Gutwein Paul,
AbdelBakky Mohamed Sadek,
Doberstein Kai,
Schramme Anja,
Beckmann Janet,
Schaefer Liliana,
Amann Kerstin,
Doller Anke,
KämpferKolb Nicole,
AbdelAziz AbdelAziz H.,
Sayed El Sayed M. El,
Pfeilschifter Josef
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00761.x
Subject(s) - diabetic nephropathy , cxcl16 , cd36 , medicine , oxidative stress , endocrinology , fibronectin , downregulation and upregulation , chemistry , receptor , microbiology and biotechnology , biology , diabetes mellitus , chemokine , extracellular matrix , chemokine receptor , biochemistry , gene
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 α 3 ‐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 α 3 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.