Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway
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 phosp...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01224-w |
| _version_ | 1811335070210850816 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kunyu Shen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:18:34Z |
| format | Article |
| id | doaj.art-7808bc4954be4385acfca8ef7244f395 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-13T17:18:34Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-7808bc4954be4385acfca8ef7244f3952022-12-22T02:38:04ZengNature Publishing GroupCell Death Discovery2058-77162022-10-018111510.1038/s41420-022-01224-wAnnexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathwayKunyu Shen0Jinhua Miao1Qiongdan Gao2Xian Ling3Ye Liang4Qin Zhou5Qirong Song6Yuxin Luo7Qinyu Wu8Weiwei Shen9Xiaonan Wang10Xiaolong Li11Youhua Liu12Shan Zhou13Ying Tang14Lili Zhou15Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDepartment of Nephrology, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Nephrology, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Nephrology, The Third Affiliated Hospital of Southern Medical UniversityDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchDepartment of Nephrology, The Third Affiliated Hospital of Southern Medical UniversityDivision of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure ResearchAbstract 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.https://doi.org/10.1038/s41420-022-01224-w |
| spellingShingle | 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 Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway Cell Death Discovery |
| title | Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway |
| title_full | Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway |
| title_fullStr | Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway |
| title_full_unstemmed | Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway |
| title_short | Annexin A2 plays a key role in protecting against cisplatin-induced AKI through β-catenin/TFEB pathway |
| title_sort | annexin a2 plays a key role in protecting against cisplatin induced aki through β catenin tfeb pathway |
| url | https://doi.org/10.1038/s41420-022-01224-w |
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