Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis
The correlation between ubiquitin-editing enzyme A20 and E3 ubiquitin ligase ring finger protein (RNF) 168 has been reported to be critical for repair of DNA damage. This study aimed to evaluate the potential role of this regulatory interaction in the pathogenesis of lupus nephritis (LN). The expres...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2023-03-01
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| Series: | Journal of Innate Immunity |
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| Online Access: | https://www.karger.com/Article/FullText/527624 |
| _version_ | 1797828650504028160 |
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| author | Luxi Zou Ling Sun Ruixue Hua Yu Wu Linlin Sun Ting Chen |
| author_facet | Luxi Zou Ling Sun Ruixue Hua Yu Wu Linlin Sun Ting Chen |
| author_sort | Luxi Zou |
| collection | DOAJ |
| description | The correlation between ubiquitin-editing enzyme A20 and E3 ubiquitin ligase ring finger protein (RNF) 168 has been reported to be critical for repair of DNA damage. This study aimed to evaluate the potential role of this regulatory interaction in the pathogenesis of lupus nephritis (LN). The expression of RNF168 and A20 was measured in the podocytes derived from MRL/lpr murine lupus as well as patients with LN. Cell-based studies using renal podocytes bearing silenced RNF168, over-expressed A20, autophagy-related gene (Atg) 5 (a ubiquitin-like modifier), or silenced Atg5 were used to assess the effect of RNF168, A20, and Atg5 on DNA damage repair and nuclear factor kappa-B (NF-κB) activation in LN. It was found that podocyte autophagy was over-activated in LN and the abnormal podocyte autophagy led to down-regulation of A20, up-regulation of RNF168, and activation of the NF-κB. RNF168 silencing or A20 restoration inhibited activation of NF-κB pathway and promoted repair of DNA damage, where the level of autophagy was not changed. Activated A20 in podocytes weakened the promoting action of cell autophagy on RNF168. The current results suggest that RNF168 dysfunction may be involved in the pathogenesis of LN via down-regulation of A20 expression. Autophagy and RNF168 may be therapeutic targets for the prevention and treatment of LN. |
| first_indexed | 2024-04-09T13:07:46Z |
| format | Article |
| id | doaj.art-32767a3d9433494dac69639223e92605 |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-04-09T13:07:46Z |
| publishDate | 2023-03-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-32767a3d9433494dac69639223e926052023-05-12T11:50:28ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282023-03-0115142844110.1159/000527624527624Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus NephritisLuxi Zou0https://orcid.org/0000-0002-7289-2234Ling Sun1Ruixue Hua2Yu Wu3Linlin Sun4Ting Chen5School of Management, Xuzhou Medical University, Xuzhou, ChinaDivision of Nephrology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, ChinaDepartment of Clinical Medicine, Xuzhou Medical University, Xuzhou, ChinaDepartment of Clinical Medicine, Xuzhou Medical University, Xuzhou, ChinaDivision of Nephrology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, ChinaDivision of Nephrology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, ChinaThe correlation between ubiquitin-editing enzyme A20 and E3 ubiquitin ligase ring finger protein (RNF) 168 has been reported to be critical for repair of DNA damage. This study aimed to evaluate the potential role of this regulatory interaction in the pathogenesis of lupus nephritis (LN). The expression of RNF168 and A20 was measured in the podocytes derived from MRL/lpr murine lupus as well as patients with LN. Cell-based studies using renal podocytes bearing silenced RNF168, over-expressed A20, autophagy-related gene (Atg) 5 (a ubiquitin-like modifier), or silenced Atg5 were used to assess the effect of RNF168, A20, and Atg5 on DNA damage repair and nuclear factor kappa-B (NF-κB) activation in LN. It was found that podocyte autophagy was over-activated in LN and the abnormal podocyte autophagy led to down-regulation of A20, up-regulation of RNF168, and activation of the NF-κB. RNF168 silencing or A20 restoration inhibited activation of NF-κB pathway and promoted repair of DNA damage, where the level of autophagy was not changed. Activated A20 in podocytes weakened the promoting action of cell autophagy on RNF168. The current results suggest that RNF168 dysfunction may be involved in the pathogenesis of LN via down-regulation of A20 expression. Autophagy and RNF168 may be therapeutic targets for the prevention and treatment of LN.https://www.karger.com/Article/FullText/527624lupus nephritisa20rnf168nf-κbautophagypodocytesdna damage |
| spellingShingle | Luxi Zou Ling Sun Ruixue Hua Yu Wu Linlin Sun Ting Chen Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis Journal of Innate Immunity lupus nephritis a20 rnf168 nf-κb autophagy podocytes dna damage |
| title | Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis |
| title_full | Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis |
| title_fullStr | Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis |
| title_full_unstemmed | Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis |
| title_short | Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF-κB Activation in Lupus Nephritis |
| title_sort | degradation of ubiquitin editing enzyme a20 following autophagy activation promotes rnf168 nuclear translocation and nf κb activation in lupus nephritis |
| topic | lupus nephritis a20 rnf168 nf-κb autophagy podocytes dna damage |
| url | https://www.karger.com/Article/FullText/527624 |
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