Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation
Renal ischemia-reperfusion injury (IRI) after renal transplantation often leads to the loss of kidney graft function. However, there is still a lack of efficient regimens to prevent or alleviate renal IRI. Our study focused on the renoprotective effect of 3-Deazaneplanocin A (DZNep), which is a hist...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2020.00305/full |
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| author | Jiawei Li Jiawei Li Yue Qiu Yue Qiu Long Li Jiyan Wang Jiyan Wang Yin Celeste Cheuk Yin Celeste Cheuk Ruirui Sang Yichen Jia Yichen Jia Jina Wang Jina Wang Yi Zhang Yi Zhang Ruiming Rong Ruiming Rong |
| author_facet | Jiawei Li Jiawei Li Yue Qiu Yue Qiu Long Li Jiyan Wang Jiyan Wang Yin Celeste Cheuk Yin Celeste Cheuk Ruirui Sang Yichen Jia Yichen Jia Jina Wang Jina Wang Yi Zhang Yi Zhang Ruiming Rong Ruiming Rong |
| author_sort | Jiawei Li |
| collection | DOAJ |
| description | Renal ischemia-reperfusion injury (IRI) after renal transplantation often leads to the loss of kidney graft function. However, there is still a lack of efficient regimens to prevent or alleviate renal IRI. Our study focused on the renoprotective effect of 3-Deazaneplanocin A (DZNep), which is a histone methylation inhibitor. We found that DZNep significantly alleviated renal IRI by suppressing nuclear factor kappa-B (NF-κB), thus inhibiting the expression of inflammatory factors in renal tubular epithelial cells in vivo or in vitro. After treatment with DZNep, T cell activation was impaired in the spleen and kidney, which correlated with the downregulated expression of T-cell immunoglobulin mucin (TIM)-1 on T cells and TIM-4 in macrophages. In addition, pretreatment with DZNep was not sufficient to protect the kidney, while administration of DZNep from before to after surgery significantly ameliorated IRI. Our findings suggest that DZNep can be a novel strategy for preventing renal IRI following kidney transplantation. |
| first_indexed | 2024-12-20T20:59:07Z |
| format | Article |
| id | doaj.art-78dae9e3413e4e3d8a4e614a852aa8da |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-20T20:59:07Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-78dae9e3413e4e3d8a4e614a852aa8da2022-12-21T19:26:46ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-07-01710.3389/fmed.2020.00305529729Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell ActivationJiawei Li0Jiawei Li1Yue Qiu2Yue Qiu3Long Li4Jiyan Wang5Jiyan Wang6Yin Celeste Cheuk7Yin Celeste Cheuk8Ruirui Sang9Yichen Jia10Yichen Jia11Jina Wang12Jina Wang13Yi Zhang14Yi Zhang15Ruiming Rong16Ruiming Rong17Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaBiomedical Research Center, Institute for Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaRenal ischemia-reperfusion injury (IRI) after renal transplantation often leads to the loss of kidney graft function. However, there is still a lack of efficient regimens to prevent or alleviate renal IRI. Our study focused on the renoprotective effect of 3-Deazaneplanocin A (DZNep), which is a histone methylation inhibitor. We found that DZNep significantly alleviated renal IRI by suppressing nuclear factor kappa-B (NF-κB), thus inhibiting the expression of inflammatory factors in renal tubular epithelial cells in vivo or in vitro. After treatment with DZNep, T cell activation was impaired in the spleen and kidney, which correlated with the downregulated expression of T-cell immunoglobulin mucin (TIM)-1 on T cells and TIM-4 in macrophages. In addition, pretreatment with DZNep was not sufficient to protect the kidney, while administration of DZNep from before to after surgery significantly ameliorated IRI. Our findings suggest that DZNep can be a novel strategy for preventing renal IRI following kidney transplantation.https://www.frontiersin.org/article/10.3389/fmed.2020.00305/fullrenal IRIDZNepTIM-1T cellsNF-κB |
| spellingShingle | Jiawei Li Jiawei Li Yue Qiu Yue Qiu Long Li Jiyan Wang Jiyan Wang Yin Celeste Cheuk Yin Celeste Cheuk Ruirui Sang Yichen Jia Yichen Jia Jina Wang Jina Wang Yi Zhang Yi Zhang Ruiming Rong Ruiming Rong Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation Frontiers in Medicine renal IRI DZNep TIM-1 T cells NF-κB |
| title | Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation |
| title_full | Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation |
| title_fullStr | Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation |
| title_full_unstemmed | Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation |
| title_short | Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation |
| title_sort | histone methylation inhibitor dznep ameliorated the renal ischemia reperfusion injury via inhibiting tim 1 mediated t cell activation |
| topic | renal IRI DZNep TIM-1 T cells NF-κB |
| url | https://www.frontiersin.org/article/10.3389/fmed.2020.00305/full |
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