RRC ID 57379
Author Kurashige T, Nakajima Y, Shimamura M, Matsuyama M, Yamada M, Nakashima M, Nagayama Y.
Title Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice.
Journal Endocrinology
Abstract Autophagy is a catabolic process that involves the degradation of cellular components through the lysosomal machinery, relocating nutrients from unnecessary processes to more pivotal processes required for survival. It has been reported that systemic disruption of the Atg5 or Atg7 gene, a component of autophagy, is lethal and that its tissue-specific disruption causes tissue degeneration in several organs. However, the functional significance of autophagy in the thyroid glands remains unknown. Our preliminary data imply the possible involvement of dysfunctional autophagy in radiation-induced thyroid carcinogenesis. Therefore, we evaluated the effect of Atg5 gene knockout (KO) on thyroid morphology and function. To this end, Atg5flox/flox mice were crossed with TPO-Cre mice, yielding the thyroid follicular epithelial cell (thyrocyte)‒specific ATG5-deficient mice (Atg5thyr-KO/KO). Atg5 gene KO was confirmed by a lack of ATG5 expression, and disruption of autophagy was demonstrated by a decrease in microtubule-associated protein 1 light chain 3-II puncta and an increase in p62. Atg5thyr-KO/KO mice were born normally, and thyroid morphology, thyroid weights, and serum T4 and TSH levels were almost normal at 4 months. However, at 8 and 12 months, a decrease in the number of thyrocytes and an increase in TUNEL+-thyrocytes were observed in Atg5thyr-KO/KO mice even though thyroid function was still normal. The number of irregularly shaped (gourd-shaped) follicles was also increased. Excess oxidative stress was indicated by increased 8-hydroxy-2'-deoxyguanosine and 53BP1 foci in Atg5thyr-KO/KO mice. These data demonstrate that thyrocytes gradually undergo degradation/cell death in the absence of basal levels of autophagy, indicating that autophagy is critical for the quality control of thyrocytes.
Volume 160(9)
Pages 2085-2092
Published 2019-9-1
DOI 10.1210/en.2019-00312
PII 5532589
PMID 31314096
MeSH 8-Hydroxy-2'-Deoxyguanosine / analysis Animals Autophagy / physiology* Autophagy-Related Protein 5 / physiology Cell Death Epithelial Cells / pathology Mice Mice, Knockout Reactive Oxygen Species / metabolism Thyroid Epithelial Cells / pathology*
IF 3.8
Times Cited 4
Mice RBRC02975