Renal endoplasmic reticulum stress is coupled to impaired autophagy in a mouse model of GSD Ia

Mol Genet Metab. 2017 Nov;122(3):95-98. doi: 10.1016/j.ymgme.2017.08.013. Epub 2017 Sep 1.

Abstract

GSD Ia (von Gierke Disease, Glycogen Storage Disease Type Ia) is a devastating genetic disorder with long-term sequelae, such as non-alcoholic fatty liver disease and renal failure. Down-regulated autophagy is involved in the development of hepatic metabolic dysfunction in GSD Ia; however, the role of autophagy in the renal pathology is unknown. Here we show that autophagy is impaired and endoplasmic reticulum (ER) stress is increased in the kidneys of a mouse model of GSD Ia. Induction of autophagy by rapamycin also reduces this ER stress. Taken together, these results show an additional role for autophagy down-regulation in the pathogenesis of GSD Ia, and provide further justification for the use of autophagy modulators in GSD Ia.

Keywords: Autophagy; ER stress; GSD Ia; Glucose-6-phosphatase; Glucose-6-phosphate; Glycogen storage disease type I; Kidney; Rapamycin; Von Gierke's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / genetics*
  • Disease Models, Animal
  • Down-Regulation
  • Endoplasmic Reticulum Stress / drug effects
  • Endoplasmic Reticulum Stress / genetics*
  • Glucose-6-Phosphatase / metabolism
  • Glucose-6-Phosphate / metabolism
  • Glycogen Storage Disease Type I / complications
  • Glycogen Storage Disease Type I / genetics
  • Glycogen Storage Disease Type I / physiopathology*
  • Immunosuppressive Agents / pharmacology
  • Kidney / pathology*
  • Mice
  • Sirolimus / pharmacology

Substances

  • Immunosuppressive Agents
  • Glucose-6-Phosphate
  • Glucose-6-Phosphatase
  • Sirolimus