P2X7 receptor inhibition attenuates podocyte injury by oxLDL through deregulating CXCL16

Abstract

This study aims to evaluate the effect of purinergic ligand-gated ion channel 7 receptor (P2X7R) antagonist A438079 in kidneys of children with primary nephrotic syndrome (PNS). In vitro, human podocytes were respectively stimulated with oxLDL (80 µg/ml), A438079 (10 µmol/L), or the compound oxLDL and A438079 together.CXC chemokine ligand 16 (CXCL16) and P2X7R expression levels were detected by Western blot and immunofluorescence assay, respectively. Immunofluorescence assay was used to detect Dil-oxLDL, and a Colorimetric Cholesterol Detection Kit was used for quantitative determination. Our results demonstrated that CXCL16 and P2X7R expression levels were remarkably increased in the renal tissue from children with PNS, particularly in the same location. Furthermore, in contrast to children with minimal change disease, the expressions of P2X7R and CXCL16 in renal tissue of children with focal segmental glomerulosclerosis were more obvious. In vitro, CXCL16 and P2X7R expression levels in human podocytes stimulated with oxLDL were markedly elevated accompanying higher intracellular lipid accumulation compared with the normal control group. In addition, pretreatment of human podocytes with A438079 before the start of oxLDL stimulation causes a significant reduction in CXCL16 expression and a decrease in lipid accumulation. Overall, CXCL16 and P2X7R may participate in the progression of PNS. The lipid accumulation reduction caused by A438079 may be through deregulating the CXCL16 pathway, suggesting that there is a potential role for P2X7R antagonists to remedy PNS.

Human In Vitro Oxidized Low-Density Lipoprotein (oxLDL) Increases Urinary Albumin Excretion in Rats

“…It is generally accepted that oxidative modification of LDL results in loss of recognition by the LDL receptor and a shift to recognition by scavenger receptors, which do not have reduced surface expression when exposed to excess cholesterol [7]. It has been observed that scavenger receptors like CXCL16 are expressed on podocytes and may play a role in their apoptosis [8,9]. There is considerable evidence that oxLDL is a critical factor in the development of atherosclerosis and renal disease.…”