Suppressor of cytokine signaling-1 reduces high glucose-induced TGF-beta1 and fibronectin synthesis in human mesangial cells

FEBS Lett. 2008 Oct 15;582(23-24):3484-8. doi: 10.1016/j.febslet.2008.09.014. Epub 2008 Sep 16.

Abstract

Janus kinase (JAK) signal transducers, and activators of transcription (STAT), contribute to diabetic nephropathy. Here we show that one of the suppressors of cytokine signaling (SOCS) proteins, SOCS-1, was upregulated in human mesangial cells (HMCs) under high glucose conditions, along with the activation of JAK2, STAT1, and STAT3. Overexpression of SOCS-1 in HMCs inhibited HG-induced JAK2/STAT activation, c-Fos/c-Jun expression, and increased synthesis of TGF-beta1 and fibronectin. These data suggest that SOCS-1 inhibits HG-induced overexpression of TGF-beta1 and synthesis of fibronectin in HMC, which may be via JAK/STAT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fibronectins / antagonists & inhibitors*
  • Fibronectins / biosynthesis
  • Glucose / metabolism*
  • Humans
  • Janus Kinase 2 / metabolism
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / antagonists & inhibitors
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-jun / antagonists & inhibitors
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / biosynthesis
  • Tyrosine / metabolism

Substances

  • Fibronectins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • SOCS1 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transforming Growth Factor beta1
  • Tyrosine
  • JAK2 protein, human
  • Janus Kinase 2
  • Glucose