OxLDL promotes podocyte migration by regulating CXCL16, ADAM10 and ACTN4

Abstract

Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in the pediatric population. Hyperlipidemia is one of the main features of NS. The present study investigated the role of CXC motif chemokine ligand 16 (CXCL 16) and ADAM metallopeptidase domain 10 (ADAM10) in oxidized low-density lipoprotein (oxLDL )-stimualted podocytes and the underlying mechanisms. CXCL 16 and ADA M10 expression levels in oxLDL. treated podocytes were measured via reverse transcription-quantitative PCR and western blotting. Cell migration assays were conducted to assess the migration of oxLDL. treated podocytes. CXCL 16 or ADA M10 overexpression and knockdown assays were conducted. The results indicated that oxLDL stimulation increased ADA M10 and CXCL 16 expression levels, and enhanced podocyte migration compared with the control group. Moreover, CXCL 16 and ADA M10 overexpression significantly increased podocyte migration and the expression of actinin-α4 (AC TN4) compared with the control groups. By contrast, CXCL 16 and ADA M10 knockdown significantly reduced podocyte migration and the expression of AC TN4 compared with the control groups. The results suggested that oxLDL promoted podocyte migration by regulating CXCL 16 and ADA M10 expression, as well as by modulating the actin cytoskeleton. Therefore, CXCL 16 and ADA M10 may serve as novel therapeutic targets for primary nephrotic syndrome in children.