Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

1 Scopus Citations
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Author(s)

  • Yan Li
  • Dongmei Zhou
  • Yinghui Ren
  • Zimu Zhang
  • Xiangdong Guo
  • MingKun Ma
  • Zhenyi Xue
  • Jienv Lv
  • Hongkun Liu
  • Qing Xi
  • Long Jia
  • Lijuan Zhang
  • Ying Liu
  • Qi Zhang
  • Jun Yan
  • Yurong Da
  • Fei Gao
  • Zhi Yao
  • Rongxin Zhang

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)478–492
Journal / PublicationAutophagy
Volume15
Issue number3
Early online date13 Sep 2018
Publication statusPublished - 2019

Link(s)

Abstract

Microglia are innate immune cells in the central nervous system (CNS), that supplies neurons with key factors for executing autophagosomal/lysosomal functions. Macroautophagy/autophagy is a cellular catabolic process that maintains cell balance in response to stress-related stimulation. Abnormal autophagy occurs with many pathologies, such as cancer, and autoimmune and neurodegenerative diseases. Hence, clarification of the mechanisms of autophagy regulation is of utmost importance. Recently, researchers presented microRNAs (miRNAs) as novel and potent modulators of autophagic activity. Here, we found that Mir223 deficiency significantly ameliorated CNS inflammation, demyelination and the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) and increased resting microglia and autophagy in brain microglial cells. In contrast, the autophagy inhibitor 3-methylademine (3-MA) aggravated the clinical symptoms of EAE in wild-type (WT) and Mir223-deficienct mice. Furthermore, it was confirmed that Mir223 deficiency in mice increased the protein expression of ATG16L1 (autophagy related 16-like 1 [S. cerevisiae]) and LC3-II in bone marrow-derived macrophage cells compared with cells from WT mice. Indeed, the cellular level of Atg16l1 was decreased in BV2 cells upon Mir223 overexpression and increased following the introduction of antagomirs. We also showed that the 3’ UTR of Atg16l1 contained functional Mir223-responsive sequences and that overexpression of ATG16L1 returned autophagy to normal levels even in the presence of Mir223 mimics. Collectively, these data indicate that Mir223 is a novel and important regulator of autophagy and that Atg16l1 is a Mir223 target in this process, which may have implications for improving our understanding of the neuroinflammatory process of EAE.

Research Area(s)

  • ATG16L1, autophagy, CNS inflammation, experimental autoimmune encephalomyelitis, microglia, Mir223

Citation Format(s)

Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1. / Li, Yan; Zhou, Dongmei; Ren, Yinghui; Zhang, Zimu; Guo, Xiangdong; Ma, MingKun; Xue, Zhenyi; Lv, Jienv; Liu, Hongkun; Xi, Qing; Jia, Long; Zhang, Lijuan; Liu, Ying; Zhang, Qi; Yan, Jun; Da, Yurong; Gao, Fei; Yue, Jianbo; Yao, Zhi; Zhang, Rongxin.

In: Autophagy, Vol. 15, No. 3, 2019, p. 478–492.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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