Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl-2 and p53 pathways

J Cell Biochem. 2013 May;114(5):1029-38. doi: 10.1002/jcb.24442.

Abstract

Recent studies have shown that Notch pathway plays a key role in the pathogenesis of diabetic nephropathy (DN), however, the exact mechanisms remain elusive. Here we demonstrated that high glucose (HG) upregulated Notch pathway in podocytes accompanied with the alteration of Bcl-2 and p53 pathways, subsequently leading to podocytes apoptosis. Inhibition of Notch pathway by chemical inhibitor or specific short hairpin RNA (shRNA) vector in podocytes prevented Bcl-2- and p53-dependent cell apoptosis. These findings suggest that Notch pathway mediates HG-induced podocytes apoptosis via Bcl-2 and p53 pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Calcium-Binding Proteins / metabolism
  • Gene Knockdown Techniques
  • Glucose / pharmacology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Podocytes / drug effects
  • Podocytes / metabolism
  • Podocytes / pathology*
  • Protease Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering / metabolism
  • Receptors, Notch / metabolism*
  • Serrate-Jagged Proteins
  • Signal Transduction / drug effects*
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Protease Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • Tumor Suppressor Protein p53
  • Amyloid Precursor Protein Secretases
  • Glucose