LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress
Abstract According to the World Health Organization, more than 12% of the world’s population suffers from noise-induced hearing loss (NIHL). Oxidative stress-mediated damage to the stria vascularis (SV) is one of the pathogenic mechanisms of NIHL. Recent studies indicate that glycolysis plays a crit...
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| Format: | Article |
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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/s41419-025-07394-6 |
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| author | Ying Yi Min-Yu Wu Kai-Tian Chen An-Hai Chen Lin-Qiu Li Qin Xiong Xian-Ren Wang Wen-Bin Lei Guan-Xia Xiong Shu-Bin Fang |
| author_facet | Ying Yi Min-Yu Wu Kai-Tian Chen An-Hai Chen Lin-Qiu Li Qin Xiong Xian-Ren Wang Wen-Bin Lei Guan-Xia Xiong Shu-Bin Fang |
| author_sort | Ying Yi |
| collection | DOAJ |
| description | Abstract According to the World Health Organization, more than 12% of the world’s population suffers from noise-induced hearing loss (NIHL). Oxidative stress-mediated damage to the stria vascularis (SV) is one of the pathogenic mechanisms of NIHL. Recent studies indicate that glycolysis plays a critical role in endothelial cells (ECs)-related diseases. However, the specific role of glycolysis in dysfunction of SV-ECs remain largely unknown. In this study, we investigated the effects of glycolysis on SV-ECs in vitro and on the SV in vivo. Our previous research identified the glycolysis pathway as a potential mechanism underlying the SV-ECs injuries induced by oxidative stress. We further examined the expression levels of glycolytic genes in SV-ECs under H2O2 stimulation and in noise-exposed mice. We found that the gene and protein expression levels of glycolytic-related enzyme LDHA significantly decreased at early phase after oxidative stress injury both in vitro and in vivo, and exhibited anti-inflammatory effects on macrophages (Mφ). Moreover, we analyzed the differential secretomes of SV-ECs with and without inhibition of LDHA using LC-MS/MS technology, identifying CX3CL1 as a candidate mediator for cellular communication between SV-ECs and Mφ. We found that CX3CL1 secretion from SV-ECs was decreased following LDHA inhibition and exhibited anti-inflammatory effects on Mφ via the CX3CR1 pathway. Similarly, the pro-inflammatory effect of LDHA-overexpressing SV-ECs was attenuated following inhibition of CX3CL1. In conclusion, our study revealed that glycolysis-related LDHA was reduced in oxidative stress-induced SV-ECs, and that LDHA inhibition in SV-ECs elicited anti-inflammatory effects on Mφ, at least partially through the CX3CL1-CX3CR1 pathway. These findings suggest that LDHA represent a novel therapeutic strategy for the treatment of NIHL. |
| format | Article |
| id | doaj-art-62be02303e9144aa82f0c54d9d845897 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-62be02303e9144aa82f0c54d9d8458972025-02-09T12:56:52ZengNature Publishing GroupCell Death and Disease2041-48892025-02-0116111210.1038/s41419-025-07394-6LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stressYing Yi0Min-Yu Wu1Kai-Tian Chen2An-Hai Chen3Lin-Qiu Li4Qin Xiong5Xian-Ren Wang6Wen-Bin Lei7Guan-Xia Xiong8Shu-Bin Fang9Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityOtorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract According to the World Health Organization, more than 12% of the world’s population suffers from noise-induced hearing loss (NIHL). Oxidative stress-mediated damage to the stria vascularis (SV) is one of the pathogenic mechanisms of NIHL. Recent studies indicate that glycolysis plays a critical role in endothelial cells (ECs)-related diseases. However, the specific role of glycolysis in dysfunction of SV-ECs remain largely unknown. In this study, we investigated the effects of glycolysis on SV-ECs in vitro and on the SV in vivo. Our previous research identified the glycolysis pathway as a potential mechanism underlying the SV-ECs injuries induced by oxidative stress. We further examined the expression levels of glycolytic genes in SV-ECs under H2O2 stimulation and in noise-exposed mice. We found that the gene and protein expression levels of glycolytic-related enzyme LDHA significantly decreased at early phase after oxidative stress injury both in vitro and in vivo, and exhibited anti-inflammatory effects on macrophages (Mφ). Moreover, we analyzed the differential secretomes of SV-ECs with and without inhibition of LDHA using LC-MS/MS technology, identifying CX3CL1 as a candidate mediator for cellular communication between SV-ECs and Mφ. We found that CX3CL1 secretion from SV-ECs was decreased following LDHA inhibition and exhibited anti-inflammatory effects on Mφ via the CX3CR1 pathway. Similarly, the pro-inflammatory effect of LDHA-overexpressing SV-ECs was attenuated following inhibition of CX3CL1. In conclusion, our study revealed that glycolysis-related LDHA was reduced in oxidative stress-induced SV-ECs, and that LDHA inhibition in SV-ECs elicited anti-inflammatory effects on Mφ, at least partially through the CX3CL1-CX3CR1 pathway. These findings suggest that LDHA represent a novel therapeutic strategy for the treatment of NIHL.https://doi.org/10.1038/s41419-025-07394-6 |
| spellingShingle | Ying Yi Min-Yu Wu Kai-Tian Chen An-Hai Chen Lin-Qiu Li Qin Xiong Xian-Ren Wang Wen-Bin Lei Guan-Xia Xiong Shu-Bin Fang LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress Cell Death and Disease |
| title | LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress |
| title_full | LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress |
| title_fullStr | LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress |
| title_full_unstemmed | LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress |
| title_short | LDHA-mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through CX3CL1-CX3CR1 pathway in noise-induced oxidative stress |
| title_sort | ldha mediated glycolysis in stria vascularis endothelial cells regulates macrophages function through cx3cl1 cx3cr1 pathway in noise induced oxidative stress |
| url | https://doi.org/10.1038/s41419-025-07394-6 |
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