Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts
Abstract The Glucocorticoid-induced posterior subcapsular cataracts (GIC) is a common complication of patients received glucocorticoid treatment in clinic. We find that dexamethasone (DEX) induces lens epithelial cells’ ferroptosis. DEX treatment increases intracellular ferroptosis signatures in len...
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08067-y |
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| author | Yuhang Zhang Wei Si Yi Mao Su Xu Fuzhen Li Jingjing Liu Shanshan Du Jingzhi Shao Ying Qi Xuyan Peng Mengjiao Xue Mingjun Jiang Keyu Guo Yanzhong Hu Fengyan Zhang |
| author_facet | Yuhang Zhang Wei Si Yi Mao Su Xu Fuzhen Li Jingjing Liu Shanshan Du Jingzhi Shao Ying Qi Xuyan Peng Mengjiao Xue Mingjun Jiang Keyu Guo Yanzhong Hu Fengyan Zhang |
| author_sort | Yuhang Zhang |
| collection | DOAJ |
| description | Abstract The Glucocorticoid-induced posterior subcapsular cataracts (GIC) is a common complication of patients received glucocorticoid treatment in clinic. We find that dexamethasone (DEX) induces lens epithelial cells’ ferroptosis. DEX treatment increases intracellular ferroptosis signatures in lens epithelial cell line in vitro as well as in rat lens in vivo. The inhibition of ferroptosis by liproxstatin-1 reduces the incidence of DEX-induced rat GIC. Experimental evidence and expression profiling showed that DEX induces ferroptosis through upregulating tetraspanin CD82- controlled P53 expression. DEX-activated glucocorticoid receptors directly bind to the CD82 promoter, driving its transcriptional upregulation. CD82 expression is upregulated in the anterior capsular epithelium of GIC patients as well as in the DEX-treated rat lens and caused the cell death of anterior capsule. DEX treatment and Overexpression of CD82 in cells recapitulated ferroptotic signatures through P53 activation and GPX4/SLC7A11 suppression. Taken together, GIC is closely associated with the upregulation of CD82-P53-GPX4/SLC7A11 axis-mediated ferroptosis. |
| format | Article |
| id | doaj-art-acaa2ca18f7b4dab9c43da1ba3fd083e |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-acaa2ca18f7b4dab9c43da1ba3fd083e2025-08-20T03:18:31ZengNature PortfolioCommunications Biology2399-36422025-04-018111510.1038/s42003-025-08067-yUpregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataractsYuhang Zhang0Wei Si1Yi Mao2Su Xu3Fuzhen Li4Jingjing Liu5Shanshan Du6Jingzhi Shao7Ying Qi8Xuyan Peng9Mengjiao Xue10Mingjun Jiang11Keyu Guo12Yanzhong Hu13Fengyan Zhang14The Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityThe Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityAbstract The Glucocorticoid-induced posterior subcapsular cataracts (GIC) is a common complication of patients received glucocorticoid treatment in clinic. We find that dexamethasone (DEX) induces lens epithelial cells’ ferroptosis. DEX treatment increases intracellular ferroptosis signatures in lens epithelial cell line in vitro as well as in rat lens in vivo. The inhibition of ferroptosis by liproxstatin-1 reduces the incidence of DEX-induced rat GIC. Experimental evidence and expression profiling showed that DEX induces ferroptosis through upregulating tetraspanin CD82- controlled P53 expression. DEX-activated glucocorticoid receptors directly bind to the CD82 promoter, driving its transcriptional upregulation. CD82 expression is upregulated in the anterior capsular epithelium of GIC patients as well as in the DEX-treated rat lens and caused the cell death of anterior capsule. DEX treatment and Overexpression of CD82 in cells recapitulated ferroptotic signatures through P53 activation and GPX4/SLC7A11 suppression. Taken together, GIC is closely associated with the upregulation of CD82-P53-GPX4/SLC7A11 axis-mediated ferroptosis.https://doi.org/10.1038/s42003-025-08067-y |
| spellingShingle | Yuhang Zhang Wei Si Yi Mao Su Xu Fuzhen Li Jingjing Liu Shanshan Du Jingzhi Shao Ying Qi Xuyan Peng Mengjiao Xue Mingjun Jiang Keyu Guo Yanzhong Hu Fengyan Zhang Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts Communications Biology |
| title | Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts |
| title_full | Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts |
| title_fullStr | Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts |
| title_full_unstemmed | Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts |
| title_short | Upregulation of ferroptosis in glucocorticoids-induced posterior subcapsular cataracts |
| title_sort | upregulation of ferroptosis in glucocorticoids induced posterior subcapsular cataracts |
| url | https://doi.org/10.1038/s42003-025-08067-y |
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