|
KMID : 1102220160350040212
|
|
Kidney Research and Clinical Practice
2016 Volume.35 No. 4 p.212 ~ p.218
|
|
|
The role of local IL6/JAK2/STAT3 signaling in high glucose?induced podocyte hypertrophy
|
|
Jo Hyung-Ah
Kim Joo-Young
Yang Seung-Hee
Han Seung-Seok
Joo Kwon-Wook
Kim Yon-Su
Kim Dong-Ki
|
|
|
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.
Conclusion: IL6 might play a prominent role in the local activation of JAK2/STAT3 in podocyte hypertrophy under HG conditions. In vivo studies examining this pathway are warranted.
|
|
|
KEYWORD
|
|
|
Diabetic nephropathy, Hypertrophy, Interleukin-6, JAK2/STAT3, Podocytes
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
   
|