Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways

Yan,Chufan; Zhao,Jiangyue; Qin,Yu; Zhao,Fangkun; Ji,Liyang; Zhang,Jinsong

doi:10.3892/mmr.2020.11205

Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways

Authors:
- Chufan Yan
- Jiangyue Zhao
- Yu Qin
- Fangkun Zhao
- Liyang Ji
- Jinsong Zhang
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Affiliations: Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110059, P.R. China
Published online on: June 2, 2020 https://doi.org/10.3892/mmr.2020.11205
Pages: 1295-1302
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autophagy is a major intracellular degradation system that plays an important role in several biological processes. Although some studies indicate that autophagy may play a role in lens degradation and cataracts formation, its underlying mechanism remains to be elucidated. Autophagy‑related gene 4a (ATG4a) cleaves autophagy‑related protein 8 (Atg8) near the C terminus, allowing Atg8 to conjugate with phosphatidylethanolamine via the exposed glycine; although this is pivotal in cancer development, no study has yet linked it to eye diseases. In the present study, the protein expression of ATG4a is significantly upregulated in hydrogen peroxide‑treated lens epithelial cells (HLE‑B3), indicating that ATG4a may play an important role in lens degradation. ATG4a was overexpressed using lentivirus in lens epithelial cells to observe the effect of ATG4a on various phenotypes by transmission electron microscopy, western blotting, EdU incorporation assay, flow cytometry and in situ cell death detection. The results demonstrated that the overexpression of ATG4a could promote autophagy by promoting the adenosine 5'‑monophosphate‑activated protein kinase pathway and inhibiting the Akt pathway. It also upregulated the proliferation and downregulated the apoptosis of lens epithelial cells. Overall, the present study showed that ATG4a plays a vital role in lens degradation and that it could be a potential target in cataract therapies.

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