Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR
AbstractCisplatin (DDP) is a potent chemotherapeutic; however, it can also cause acute kidney injury (AKI). Because of the complexity of the toxicity it induces, few effective methods exist for ameliorating any form of DDP-induced AKI. Recent research has suggested that the complement system is a po...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2023.2248267 |
| _version_ | 1797434310227132416 |
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| author | Zhouyu Wen Can Sun Yan Lou Juan Kong |
| author_facet | Zhouyu Wen Can Sun Yan Lou Juan Kong |
| author_sort | Zhouyu Wen |
| collection | DOAJ |
| description | AbstractCisplatin (DDP) is a potent chemotherapeutic; however, it can also cause acute kidney injury (AKI). Because of the complexity of the toxicity it induces, few effective methods exist for ameliorating any form of DDP-induced AKI. Recent research has suggested that the complement system is a potential molecular target for such amelioration. In the study here, in vivo (male ICR mice) and in vitro (HK-2 cells) models of DDP-induced AKI were established to investigate the potential therapeutic effects of Vitamin D (VD) against this form of AKI. Endpoints assessed in vivo/in vitro included overall renal function, degree of renal damage, and complement receptor C5aR expression using histology, immunohistochemistry, immunofluorescence, RT-PCR, and Western blots. The data indicated that the use of VD treatment could reduce renal pathological damage along with expression of TNFα, IL-1β, IL-18, and C5aR; however, an over-expression of C5aR weakened the protective effects of VD/VD receptor (VDR) against oxidative damage and inflammatory cell infiltration. Using a luciferase reporter gene assay and ChIP analysis, it was demonstrated that C5aR was transcriptionally inhibited by VDR. In conclusion, VD/VDR could delay DDP-induced AKI by inhibiting the expression of C5aR through transcriptional regulation and reducing the production of downstream pro-inflammatory cytokines. The present study revealed the regulatory mechanism of VD/VDR in acute renal inflammation and provides new insights into its therapeutic function in DDP-induced AKI. |
| first_indexed | 2024-03-09T10:30:21Z |
| format | Article |
| id | doaj.art-aa10aada97a841d59b0445a81abb0028 |
| institution | Directory Open Access Journal |
| issn | 1547-691X 1547-6901 |
| language | English |
| last_indexed | 2024-03-09T10:30:21Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj.art-aa10aada97a841d59b0445a81abb00282023-12-01T21:19:05ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012023-12-0120110.1080/1547691X.2023.2248267Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aRZhouyu Wen0Can Sun1Yan Lou2Juan Kong3Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Computer Science, School of Intelligent Medicine, China Medical University, Shenyang, ChinaDepartment of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, ChinaAbstractCisplatin (DDP) is a potent chemotherapeutic; however, it can also cause acute kidney injury (AKI). Because of the complexity of the toxicity it induces, few effective methods exist for ameliorating any form of DDP-induced AKI. Recent research has suggested that the complement system is a potential molecular target for such amelioration. In the study here, in vivo (male ICR mice) and in vitro (HK-2 cells) models of DDP-induced AKI were established to investigate the potential therapeutic effects of Vitamin D (VD) against this form of AKI. Endpoints assessed in vivo/in vitro included overall renal function, degree of renal damage, and complement receptor C5aR expression using histology, immunohistochemistry, immunofluorescence, RT-PCR, and Western blots. The data indicated that the use of VD treatment could reduce renal pathological damage along with expression of TNFα, IL-1β, IL-18, and C5aR; however, an over-expression of C5aR weakened the protective effects of VD/VD receptor (VDR) against oxidative damage and inflammatory cell infiltration. Using a luciferase reporter gene assay and ChIP analysis, it was demonstrated that C5aR was transcriptionally inhibited by VDR. In conclusion, VD/VDR could delay DDP-induced AKI by inhibiting the expression of C5aR through transcriptional regulation and reducing the production of downstream pro-inflammatory cytokines. The present study revealed the regulatory mechanism of VD/VDR in acute renal inflammation and provides new insights into its therapeutic function in DDP-induced AKI.https://www.tandfonline.com/doi/10.1080/1547691X.2023.2248267Vitamin DC5aRcisplatinacute kidney injuryrenal inflammation |
| spellingShingle | Zhouyu Wen Can Sun Yan Lou Juan Kong Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR Journal of Immunotoxicology Vitamin D C5aR cisplatin acute kidney injury renal inflammation |
| title | Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR |
| title_full | Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR |
| title_fullStr | Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR |
| title_full_unstemmed | Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR |
| title_short | Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR |
| title_sort | vitamin d vitamin d receptor mitigates cisplatin induced acute kidney injury by down regulating c5ar |
| topic | Vitamin D C5aR cisplatin acute kidney injury renal inflammation |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2023.2248267 |
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