Overexpression of Interleukin-13 Induces Minimal-Change–Like Nephropathy in Rats

Abstract

IL-13 has been implicated in the pathogenesis of minimal-change nephrotic syndrome. This study aimed to investigate the role of IL-13 on the development of proteinuria and expression of podocyte-related genes that are associated with nephrotic syndrome. IL-13 was overexpressed in Wistar rats through transfection of a mammalian expression vector cloned with the rat IL-13 gene, into the quadriceps by in vivo electroporation. Serum IL-13, albumin, cholesterol, and creatinine and urine albumin were measured serially. Kidneys were harvested after day 70 for histology and electron microscopy. Glomerular gene expression of nephrin, podocin, dystroglycan, B7-1, and IL-13 receptor subunits were examined using real-time PCR with hybridization probes and expressed as an index against ␤-actin. Protein expression of these molecules was determined by immunofluorescence staining. The IL-13-transfected rats (n ‫؍‬ 41) showed significant albuminuria, hypoalbuminemia, and hypercholesterolemia when compared with control rats (n ‫؍‬ 17). No significant histologic changes were seen in glomeruli of IL-13-transfected rats. However, electron microscopy showed up to 80% of podocyte foot process fusion. Glomerular gene expression was significantly upregulated for B7-1, IL-4R␣, and IL-13R␣2 but downregulated for nephrin, podocin, and dystroglycan. Immunofluorescence staining intensity was reduced for nephrin, podocin, and dystroglycan but increased for B7-1 and IL-4R␣ in IL-13-transfected rats compared with controls. In conclusion, these results suggest that IL-13 overexpression in the rat could lead to podocyte injury with downregulation of nephrin, podocin, and dystroglycan and a concurrent upregulation of B7-1 in the glomeruli, inducing a minimal change-like nephropathy that is characterized by increased proteinuria, hypoalbuminemia, hypercholesterolemia, and fusion of podocyte foot processes.

The Treatment of Minimal Change Disease in Adults

“…CD80 is also present in the podocytes of mice in MCD models and is necessary for resulting proteinuria. [7][8][9] Soluble urinary CD80 levels are elevated in children and adolescents with MCD in relapse compared with those individuals in remission, patients with other glomerular disease, and control subjects. 10 Furthermore, urinary CD80/creatinine ratios are increased in MCD in relapse compared with MCD in remission or FSGS.…”

Serum Interleukin 13 Level in Steroid Sensitive Nephrotic Syndrome

“…Thus, IL13 may injure glomerular visceral cells and increase glomerular permeability (4). Moreover, recent studies have shown that IL-13 induces the expression of CD80 by podocytes, resulting in proteinuria and epithelial cell foot process effacement (6,7).…”

Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

“…A central role for activation of the Th1 response has been proposed for some forms of collapsing FSGS (57). It remains to be determined how IFN may alter the synthesis of other, potentially pathogenic cytokines, such as IL-6 or IL-13 family members, which have been incriminated as permeability factors in FSGS and MCD (58,59). …”