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Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway

Authors :
Kunyu Shen
Jinhua Miao
Qiongdan Gao
Xian Ling
Ye Liang
Qin Zhou
Qirong Song
Yuxin Luo
Qinyu Wu
Weiwei Shen
Xiaonan Wang
Xiaolong Li
Youhua Liu
Shan Zhou
Ying Tang
Lili Zhou
Source :
Cell Death Discovery. 8
Publication Year :
2022
Publisher :
Springer Science and Business Media LLC, 2022.

Abstract

Acute kidney injury (AKI) is in high prevalence in the world. However, the therapeutic strategies for AKI are still in mystery. Studies have shown to improve autophagy and lysosomal function could inhibit AKI. But their modulators need to be explored in detail. Annexin A2 (ANXA2) is a phospholipid-binding protein involving in organelle membrane integrity function, suggesting its important role in autophagy and lysosome homeostasis. It implicates ANXA2 potentially protects against AKI. However, this has not been elucidated. Herein, we found that ANXA2 is increased in renal tubules in cisplatin-induced AKI mice. Ectopic expression of ANXA2 improved lysosomal functions and enhanced autophagic flux, further protecting against renal tubular cell apoptosis and kidney injury. Conversely, knockdown of ANXA2 inhibited lysosomal function and autophagy, which aggravated the progression of AKI. Transcriptome sequencing revealed β-catenin signaling is highly responsible for this process. In vitro, we found ANXA2 induced β-catenin activation, further triggering T-cell factor-4 (TCF4)-induced transcription factor EB (TFEB). Furthermore, TFEB promoted lysosome biogenesis to enhance autophagic flux, resulting in the alleviation of AKI. Our new findings underline ANXA2 is a new therapeutic potential for AKI through modulating autophagy and lysosomal function. The underlying mechanism is associated with its inductive effects on β-catenin/TFEB pathway.

Details

ISSN :
20587716
Volume :
8
Database :
OpenAIRE
Journal :
Cell Death Discovery
Accession number :
edsair.doi.dedup.....a038b08876402b933599b22f2369050d
Full Text :
https://doi.org/10.1038/s41420-022-01224-w