title: The role of local IL6/JAK2/STAT3 signaling in high glucose-induced podocyte hypertrophy.
abstract: BACKGROUND
  Interleukin-6 (IL6) is an important regulator of cellular hypertrophy through the gp130/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. We tested the hypothesis that IL6 and its downstream gp130/JAK2/STAT3 pathway participated in high glucose (HG)-induced podocyte hypertrophy.
  
  
  METHODS
  IL6 levels in the media and lysates of podocytes were measured by enzyme-linked immunosorbent assay. Western blots were performed to determine the protein expression levels of gp130/JAK2/STAT3 among podocytes cultured with normal glucose (NG), NG + mannitol, NG + recombinant IL6, HG, and HG + IL6-neutralizing antibodies (IL6NAb). Immunoprecipitation was examined to determine whether gp130 interacted with JAK2 in response to HG or IL6. Podocyte hypertrophy was verified using protein/cell counts and flow cytometry.
  
  
  RESULTS
  IL6 levels were significantly increased in the media and lysates of podocytes cultured in HG compared with the NG groups. The nuclear phospho-STAT3/STAT3 ratio was increased by HG and NG + IL6 and was attenuated in the HG + IL6NAb groups, indicating that nuclear STAT3 was activated following JAK2 and cytosolic STAT3 activation in response to IL6 secreted by HG-stimulated podocytes. Immunoprecipitation showed increased phospho-JAK2 recruitment to gp130 in the HG and NG + IL6 groups, and the addition of IL6NAb in the HG group significantly abrogated these increases. Podocyte hypertrophy was significantly increased in the HG and NG + IL6 compared with the NG condition and was diminished by the addition of IL6NAbs to the HG group.
  
  
  CONCLUSIONS
  IL6 might play a prominent role in the local activation of JAK2/STAT3 in podocyte hypertrophy under HG conditions.In vivostudies examining this pathway are warranted.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyung Ah
authors.initials: HA
authors.lastname: Jo
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung Seok
authors.initials: SS
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Kim
keywords: Diabetic nephropathy; Hypertrophy; Interleukin-6; JAK2/STAT3; Podocytes