title: Activation of the IL-2 Receptor in Podocytes: A Potential Mechanism for Podocyte Injury in Idiopathic Nephrotic Syndrome?
abstract: The renal podocyte plays an important role in maintaining the structural integrity of the glomerular basement membrane. We have previously reported that patients with idiopathic nephrotic syndrome (INS) have increased IL-2 production. We hypothesized that podocytes express an IL-2 receptor (IL-2R) and signaling through this receptor can result in podocyte injury. To confirm the presence of the IL-2R, we tested a conditionally immortalized murine podocyte cell line by flow cytometry, qPCR, and Western blot. To test for the presence of the IL-2R in vivo, immunohistochemical staining was performed on human renal biopsies in children with FSGS and control. Podocytes were stimulated with IL-2 in vitro, to study signaling events via the JAK/STAT pathway. The results showed that stimulation with IL-2 resulted in increased mRNA and protein expression of STAT 5a, phosphorylated STAT 5, JAK 3, and phosphorylated JAK 3. We then investigated for signs of cellular injury and the data showed that pro-apoptotic markers Bax and cFLIP were significantly increased following IL-2 exposure, whereas LC3 II was decreased. Furthermore, mitochondrial depolarization and apoptosis were both significantly increased following activation of the IL-2R. We used a paracellular permeability assay to monitor the structural integrity of a podocyte monolayer following IL-2 exposure. The results showed that podocytes exposed to IL-2 have increased albumin leakage across the monolayer. We conclude that murine podocytes express the IL-2R, and that activation through the IL-2R results in podocyte injury.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.affiliation: Department of Pediatric Nephrology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Tyrus
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Department of Research Ochsner Biobank, Ochsner Health System, New Orleans, Louisiana, United States of America.
authors.forename: Jeannine
authors.initials: J
authors.lastname: Ascani
authors.affiliation: Eurofins Central Analytical Laboratories, New Orleans, Louisiana, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tate
authors.affiliation: Department of Medical Microbiology and Immunology, American University of the Caribbean School of Medicine, Coral Gables, Florida, United States of America.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Finkel-Jimenez
authors.affiliation: Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Wilk
authors.affiliation: Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Reiss
authors.affiliation: Department of Nephrology, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Smoyer
authors.affiliation: Department of Pediatric Nephrology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Diego H
authors.initials: DH
authors.lastname: Aviles
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D002648:Child; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000378:metabolism*; D010766:Phosphorylation; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000418:Albumins; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2