Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Sequential signaling cascade of IL-6 and PGC-1alpha is involved in high glucose-induced podocyte loss and growth arrest.

Authors: Kim, DI  Park, SH 
Citation: Kim DI and Park SH, Biochem Biophys Res Commun. 2013 Jun 14;435(4):702-7. doi: 10.1016/j.bbrc.2013.05.046. Epub 2013 May 18.
Pubmed: (View Article at PubMed) PMID:23692924
DOI: Full-text: DOI:10.1016/j.bbrc.2013.05.046

Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1alpha expression, and PGC-1alpha overexpression also induced podocyte apoptosis and growth arrest. PGC-1alpha siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1alpha is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Ralpha, gp130 and PGC-1alpha may attenuate the progression of diabetic nephropathy.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 10059632
Created: 2015-08-20
Species: All species
Last Modified: 2015-08-20
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.