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Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice


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Title: Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice
Authors: Kurashige, Tomomi / Nakajima, Yasuyo / Shimamura, Mika / Matsuyama, Mutsumi / Yamada, Masanobu / Nakashima, Masahiro / Nagayama, Yuji
Issue Date: 17-Jul-2019
Publisher: Oxford University Press
Citation: Endocrinology, 160(9), pp.2085-2092; 2019
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.
Keywords: thyrocyte / autophagy / atg5 / knockout / apoptosis
URI: http://hdl.handle.net/10069/39462
DOI: 10.1210/en.2019-00312
Rights: © 2019 Endocrine Society. This is a pre-copyedited, author-produced version of an article accepted for publication in Endocrinology following peer review. The version of record Endocrinology, 160(9), pp.2085-2092; 2019 is available online at: https://doi.org/10.1210/en.2019-00312.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39462

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