Renal endoplasmic reticulum stress is coupled to impaired autophagy in a mouse model of GSD Ia
Farah B.L. ; Landau D.J. ; Wu Y. ; Sinha R.A. ; Loh A. ; Bay B.-H. ; Koeberl D.D. ; Yen P.M.
Farah B.L.
Landau D.J.
Koeberl D.D.
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Alternative Title
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. � 2017 Elsevier Inc.
Keywords
Autophagy, ER stress, Glucose-6-phosphatase, Glucose-6-phosphate, Glycogen storage disease type I, GSD Ia, Kidney, Rapamycin, Von Gierke's disease
Source Title
Molecular Genetics and Metabolism
Publisher
Academic Press Inc.
Series/Report No.
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Date
2017
DOI
10.1016/j.ymgme.2017.08.013
Type
Article