Septin 7 mediates high glucose-induced podocyte apoptosis

Biochem Biophys Res Commun. 2018 Nov 30;506(3):522-528. doi: 10.1016/j.bbrc.2018.10.081. Epub 2018 Oct 22.

Abstract

Podocyte depletion is a central pathological mechanism of diabetic nephropathy (DN). Hyperglycemia induced podocyte apoptosis, resulting in podocyte depletion. However, the crucial mechanism of hyperglycemia-induced podocyte apoptosis remains poorly understood. In this study, we evaluated the expression of septin 7, a GTP-binding protein, in glomerular podocytes of patients and mice with DN, and investigated the pro-apoptotic effect of septin 7 on high glucose (HG) induced podocyte apoptosis in vitro. We found septin 7 expression was markedly increased not only in glomerular podocytes of patients and db/db mice with DN but also in cultured podocytes with HG stimulation. Knocking down septin 7 with siRNA could attenuate HG induced podocytes apoptosis and excessive intracellular Ca2+ concentration. This study revealed septin7 may potentially play a proapoptotic role in podocyte under diabetic conditions and may provide a potential target for preventing podocyte apoptosis in DN.

Keywords: Apoptosis; Diabetic nephropathy; Podocyte; Septin 7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Calcium / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Diabetic Nephropathies / pathology
  • Gene Knockdown Techniques
  • Glucose
  • Humans
  • Intracellular Space / metabolism
  • Male
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Podocytes / metabolism*
  • Podocytes / pathology*
  • Septins / metabolism*

Substances

  • Cell Cycle Proteins
  • Microfilament Proteins
  • SYNPO protein, human
  • SEPTIN7 protein, human
  • Sept7 protein, mouse
  • Septins
  • Glucose
  • Calcium