Autophagy is involved in mouse kidney development and podocyte differentiation regulated by Notch signalling

J Cell Mol Med. 2017 Jul;21(7):1315-1328. doi: 10.1111/jcmm.13061. Epub 2017 Feb 3.

Abstract

Podocyte dysfunction results in glomerular diseases accounted for 90% of end-stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down-regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT-treated cells, and as a result, nephrin was recovered and DAPT-induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling.

Keywords: autophagy; differentiation; notch signalling; podocyte; renal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Diamines / pharmacology
  • Kidney / growth & development*
  • Membrane Proteins / genetics*
  • Mice
  • Podocytes / cytology
  • Podocytes / metabolism
  • Receptor, Notch1 / genetics*
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • Thiazoles / pharmacology

Substances

  • 24-diamino-5-phenylthiazole
  • Diamines
  • Membrane Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Thiazoles
  • nephrin
  • Sirolimus