SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1
Abstract Nuclear receptor 4A1 (NR4A1) is a gene that increases the likelihood of chronic kidney disease (CKD) and contributes to its development. Previous research has shown that the SAM pointed domain containing Ets transformation-specific transcription factor (SPDEF) can activate NR4A1, but its me...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-024-01030-3 |
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| _version_ | 1832585612866093056 |
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| author | Hongshuang Wang Ziheng Wei Chang Xu Fang Fang Zheng Wang Yan Zhong Xiangting Wang |
| author_facet | Hongshuang Wang Ziheng Wei Chang Xu Fang Fang Zheng Wang Yan Zhong Xiangting Wang |
| author_sort | Hongshuang Wang |
| collection | DOAJ |
| description | Abstract Nuclear receptor 4A1 (NR4A1) is a gene that increases the likelihood of chronic kidney disease (CKD) and contributes to its development. Previous research has shown that the SAM pointed domain containing Ets transformation-specific transcription factor (SPDEF) can activate NR4A1, but its mechanism of action in renal fibrosis is not yet clear. In this study, we used adenovirus to create a mouse kidney model with a specific knockdown of NR4A1 gene. Our results showed that the knockdown of NR4A1 can accelerate unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice, and overexpression of NR4A1 can significantly reduce transforming growth factor-β1-induced (TGF-β1) fibrosis in HK-2 cells. Additionally, we found that overexpression of SPDEF can improve UUO-induced renal fibrosis in mice and TGF-β1-induced fibrosis in HK-2 by transcriptionally activating NR4A1. These findings suggest that SPDEF can activate NR4A1 transcriptionally and improve renal fibrosis. |
| format | Article |
| id | doaj-art-07d3fffd422f47f489161d27dc727270 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-07d3fffd422f47f489161d27dc7272702025-01-26T12:38:43ZengBMCMolecular Medicine1528-36582024-12-0130111310.1186/s10020-024-01030-3SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1Hongshuang Wang0Ziheng Wei1Chang Xu2Fang Fang3Zheng Wang4Yan Zhong5Xiangting Wang6Hebei University of Chinese MedicineHebei University of Chinese MedicineHebei University of Chinese MedicineHebei University of Chinese MedicineHebei University of Chinese MedicineHebei University of Chinese MedicineHebei University of Chinese MedicineAbstract Nuclear receptor 4A1 (NR4A1) is a gene that increases the likelihood of chronic kidney disease (CKD) and contributes to its development. Previous research has shown that the SAM pointed domain containing Ets transformation-specific transcription factor (SPDEF) can activate NR4A1, but its mechanism of action in renal fibrosis is not yet clear. In this study, we used adenovirus to create a mouse kidney model with a specific knockdown of NR4A1 gene. Our results showed that the knockdown of NR4A1 can accelerate unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice, and overexpression of NR4A1 can significantly reduce transforming growth factor-β1-induced (TGF-β1) fibrosis in HK-2 cells. Additionally, we found that overexpression of SPDEF can improve UUO-induced renal fibrosis in mice and TGF-β1-induced fibrosis in HK-2 by transcriptionally activating NR4A1. These findings suggest that SPDEF can activate NR4A1 transcriptionally and improve renal fibrosis.https://doi.org/10.1186/s10020-024-01030-3Chronic kidney diseaseNR4A1SPDEFRenal fibrosis |
| spellingShingle | Hongshuang Wang Ziheng Wei Chang Xu Fang Fang Zheng Wang Yan Zhong Xiangting Wang SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 Molecular Medicine Chronic kidney disease NR4A1 SPDEF Renal fibrosis |
| title | SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 |
| title_full | SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 |
| title_fullStr | SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 |
| title_full_unstemmed | SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 |
| title_short | SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1 |
| title_sort | spdef ameliorates uuo induced renal fibrosis by transcriptional activation of nr4a1 |
| topic | Chronic kidney disease NR4A1 SPDEF Renal fibrosis |
| url | https://doi.org/10.1186/s10020-024-01030-3 |
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