p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6
Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556524000330 |
| _version_ | 1797248385828257792 |
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| author | Ying Cheng Man Zhang Rong Xu Lingli Fu Mei Xue Chaofei Xu Chao Tang Ting Fang Xiaohuan Liu Bei Sun Liming Chen |
| author_facet | Ying Cheng Man Zhang Rong Xu Lingli Fu Mei Xue Chaofei Xu Chao Tang Ting Fang Xiaohuan Liu Bei Sun Liming Chen |
| author_sort | Ying Cheng |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-β-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR. |
| first_indexed | 2024-04-24T20:13:45Z |
| format | Article |
| id | doaj.art-03a293e350254b6898991f396f84ac25 |
| institution | Directory Open Access Journal |
| issn | 1873-6815 |
| language | English |
| last_indexed | 2024-04-24T20:13:45Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj.art-03a293e350254b6898991f396f84ac252024-03-23T06:22:34ZengElsevierExperimental Gerontology1873-68152024-04-01188112391p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6Ying Cheng0Man Zhang1Rong Xu2Lingli Fu3Mei Xue4Chaofei Xu5Chao Tang6Ting Fang7Xiaohuan Liu8Bei Sun9Liming Chen10NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaCorresponding authors.; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaCorresponding authors.; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, ChinaDiabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-β-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.http://www.sciencedirect.com/science/article/pii/S0531556524000330Diabetic retinopathySenescenceSingle-cell RNA sequencingp53Ubiquitination |
| spellingShingle | Ying Cheng Man Zhang Rong Xu Lingli Fu Mei Xue Chaofei Xu Chao Tang Ting Fang Xiaohuan Liu Bei Sun Liming Chen p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 Experimental Gerontology Diabetic retinopathy Senescence Single-cell RNA sequencing p53 Ubiquitination |
| title | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 |
| title_full | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 |
| title_fullStr | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 |
| title_full_unstemmed | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 |
| title_short | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6 |
| title_sort | p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing foxo3a ubiquitylation and degradation via ube2l6 |
| topic | Diabetic retinopathy Senescence Single-cell RNA sequencing p53 Ubiquitination |
| url | http://www.sciencedirect.com/science/article/pii/S0531556524000330 |
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