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

Kin-Wai Lai^*, Chang-Li Wei^*, Li-Kiang Tan^*, Puay-Hoon Tan, Gilbert S.C. Chiang, Caroline G.L. Lee, Stanley C. Jordan and Hui-Kim Yap^*,||

Departments of ^* Pediatrics and Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Department of Pathology, Singapore General Hospital, and ^|| The Children's Medical Institute, National University Hospital, Singapore; and Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California

Address correspondence to: Dr. Hui-Kim Yap, Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074. Phone: +65-67724112; Fax: +65-67797486; paeyaphk{at}nus.edu.sg

Received for publication July 7, 2006. Accepted for publication February 14, 2007.

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-13R2 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.

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