Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction
Abstract Acute kidney injury (AKI) is in rapid prevalence nowadays. Of note, the underlying mechanisms have not been clarified. Several reports showed a cluster of differentiation-44 (CD44), a cell-surface glycoprotein, might be involved in AKI. However, its role in AKI has not been clearly clarifie...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07438-x |
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| author | Jiewu Huang Ping Meng Ye Liang Xiaolong Li Shan Zhou Jiemei Li Xiaoxu Wang Jinhua Miao Weiwei Shen Lili Zhou |
| author_facet | Jiewu Huang Ping Meng Ye Liang Xiaolong Li Shan Zhou Jiemei Li Xiaoxu Wang Jinhua Miao Weiwei Shen Lili Zhou |
| author_sort | Jiewu Huang |
| collection | DOAJ |
| description | Abstract Acute kidney injury (AKI) is in rapid prevalence nowadays. Of note, the underlying mechanisms have not been clarified. Several reports showed a cluster of differentiation-44 (CD44), a cell-surface glycoprotein, might be involved in AKI. However, its role in AKI has not been clearly clarified. Herein, we found CD44 increased in renal tubules in AKI mice. Gene ablation of CD44 improved mitochondrial biogenesis and fatty acid oxidation (FAO) function, further protecting against tubular cell death and kidney injury. Conversely, ectopic CD44 impaired mitochondrial homeostasis and exacerbated tubular cell apoptosis to aggravate AKI progression. From transcriptome sequencing, we found that CD44 induces mitogen-activated protein kinase (MAPK) and NF-κB p65 signaling. Lipidomics also showed that CD44 interfered with multiple aspects of lipid metabolism. We deeply investigated NF-κB p65 inhibited the transcription of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), resulting in mitochondrial dysfunction and cell apoptosis. CD44 also facilitated iron intake to assist cell ferroptosis. Hence, our study provided a new mechanism for AKI, and demonstrated that targeted inhibition on CD44 could be a promising therapeutic strategy to resist AKI. |
| format | Article |
| id | doaj-art-4abcdda423f14bfe980e2486f3558b3c |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-4abcdda423f14bfe980e2486f3558b3c2025-08-20T03:10:50ZengNature Publishing GroupCell Death and Disease2041-48892025-02-0116111810.1038/s41419-025-07438-xTubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunctionJiewu Huang0Ping Meng1Ye Liang2Xiaolong Li3Shan Zhou4Jiemei Li5Xiaoxu Wang6Jinhua Miao7Weiwei Shen8Lili Zhou9Division 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 Central Laboratory, Huadu District People’s Hospital of GuangzhouDivision 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 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 ResearchAbstract Acute kidney injury (AKI) is in rapid prevalence nowadays. Of note, the underlying mechanisms have not been clarified. Several reports showed a cluster of differentiation-44 (CD44), a cell-surface glycoprotein, might be involved in AKI. However, its role in AKI has not been clearly clarified. Herein, we found CD44 increased in renal tubules in AKI mice. Gene ablation of CD44 improved mitochondrial biogenesis and fatty acid oxidation (FAO) function, further protecting against tubular cell death and kidney injury. Conversely, ectopic CD44 impaired mitochondrial homeostasis and exacerbated tubular cell apoptosis to aggravate AKI progression. From transcriptome sequencing, we found that CD44 induces mitogen-activated protein kinase (MAPK) and NF-κB p65 signaling. Lipidomics also showed that CD44 interfered with multiple aspects of lipid metabolism. We deeply investigated NF-κB p65 inhibited the transcription of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), resulting in mitochondrial dysfunction and cell apoptosis. CD44 also facilitated iron intake to assist cell ferroptosis. Hence, our study provided a new mechanism for AKI, and demonstrated that targeted inhibition on CD44 could be a promising therapeutic strategy to resist AKI.https://doi.org/10.1038/s41419-025-07438-x |
| spellingShingle | Jiewu Huang Ping Meng Ye Liang Xiaolong Li Shan Zhou Jiemei Li Xiaoxu Wang Jinhua Miao Weiwei Shen Lili Zhou Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction Cell Death and Disease |
| title | Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction |
| title_full | Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction |
| title_fullStr | Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction |
| title_full_unstemmed | Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction |
| title_short | Tubular CD44 plays a key role in aggravating AKI through NF-κB p65-mediated mitochondrial dysfunction |
| title_sort | tubular cd44 plays a key role in aggravating aki through nf κb p65 mediated mitochondrial dysfunction |
| url | https://doi.org/10.1038/s41419-025-07438-x |
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