In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL

In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore VCP-Eribulin all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN. on a variety of renal cells, like mesangial cells [5C7], endothelial cells [8, 9] Rabbit Polyclonal to REN and podocytes [10]. Many important roles have been ascribed to oxLDL, which could be involved in the progression of renal diseases. It is well known that oxLDL can induce the production of chemokines and the expression of adhesion molecules on endothelial cells [11]. Furthermore, oxLDL can harm the kidney either directly, by deposition of lipids, or indirectly, by stimulating the generation of reactive oxygen species (ROS) [12, 13]. In addition to this data, several animal models have documented that chronic exposure to oxLDL promotes collagen synthesis and activates pro-inflammatory pathways [14, 15]. Moreover, oxLDL also promotes fibrosis by stimulating synthesis and expression of TGF-[16]. Beside VCP-Eribulin the important role of mesangial VCP-Eribulin cells in the onset of DN [17], accumulating data demonstrate that podocytes are functionally and structurally injured very early in the natural history of DN [18]. Therefore, in order to improve the treatment of glomerular diseases like DN the identification of new proteins involved in podocyte injury are of high importance. The loss of podocytes, also known as podocytopenia, is an important characteristic feature in diabetic patients [19C22] and beside pro-inflammatory actions of oxLDL, the cytotoxic effects of oxLDL on podocytes has been recently shown [10]. Scavenger receptors are VCP-Eribulin found on many cell lineages. They are known to bind modified lipoproteins and to promote the transformation of macrophages (M) and smooth muscle cells into foam cells [23, 24]. However, little is known about the regulation and function of scavenger receptors in normal and pathological states of the kidney. CXCL16 (SR-PSOX) is one of the few scavenger receptors that is found in two distinct forms: membrane bound and soluble. Surface-expressed CXCL16 binds and internalizes oxLDL and promotes adhesion of cells expressing its cognate receptor CXCR6 [25, 26]. In contrast soluble CXCL16 produced by proteolytic cleavage ADAM10 and ADAM17 [27, 28], acts as a chemotactic factor for CXCR6 expressing cells such as NKT and polarized T helper cells [29, 30]. Importantly, in an animal model of chronic kidney disease elevated CXCL16 levels were accompanied with increased levels of oxLDL in the onset of renal obstruction [31]. We have recently described the expression of CXCL16 and ADAM10 in human podocytes and presented evidence that CXCL16 is involved in the uptake of oxLDL in human podocytes (Gutwein CD36 and only partially involved CXCL16 (Fig. ?(Fig.1C1C and ?andD).D). Again, combined blocking of CXCL16 and CD36 inhibited the uptake of oxLDL to a VCP-Eribulin similar extent than CD36 alone (Fig. ?(Fig.1C1C and ?andD).D). Weak expression of CD36 in human podocytes was determined by confocal immunofluorescence analysis (Fig. ?(Fig.1E).1E). In contrast to CD36, stronger constitutive CXCL16 expression was detectable in human podocytes (Fig. ?(Fig.1F).1F). Taken this data together, in podocytes CXCL16 mediates mainly the uptake of oxLDL, whereas in tubular cells CD36 seems to be the main receptor for oxLDL. Open in a separate window Open in a separate window Open in a separate window Open in a separate window Figure 1 Involvement of CXCL16 and CD36 in the uptake of oxLDL..