title: 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 beta-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-4Ralpha, and IL-13Ralpha2 but downregulated for nephrin, podocin, and dystroglycan. Immunofluorescence staining intensity was reduced for nephrin, podocin, and dystroglycan but increased for B7-1 and IL-4Ralpha 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.
authors.affiliation: Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kin-Wai
authors.initials: KW
authors.lastname: Lai
authors.forename: Chang-Li
authors.initials: CL
authors.lastname: Wei
authors.forename: Li-Kiang
authors.initials: LK
authors.lastname: Tan
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Gilbert S C
authors.initials: GS
authors.lastname: Chiang
authors.forename: Caroline G L
authors.initials: CG
authors.lastname: Lee
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
authors.forename: Hui-Kim
authors.initials: HK
authors.lastname: Yap
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism; D018274:Electroporation; D005260:Female; D005786:Gene Expression Regulation; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009402:Nephrosis, Lipoid / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018122:B7-1 Antigen; C504001:Il4r protein, rat; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D053662:Interleukin-4 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin; D049030:Dystroglycans