دورية أكاديمية
Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment
| العنوان: | Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment |
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| المؤلفون: | Chen, Juntao, Xu, Cuidi, Yang, Kun, Gao, Rifeng, Cao, Yirui, Liang, Lifei, Chen, Siyue, Xu, Shihao, Rong, Ruiming, Wang, Jina, Zhu, Tongyu |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Ischemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). The role of N 6- methyladenosine (m6A) modification in AKI remains unclear. Here, we characterize the role of AlkB homolog 5 (ALKBH5) and m6A modification in an I/R-induced renal injury model in male mice. Alkbh5 -knockout mice exhibit milder pathological damage and better renal function than wild-type mice post-IRI, whereas Alkbh5 -knockin mice show contrary results. Also conditional knockout of Alkbh5 in the tubular epithelial cells alleviates I/R-induced AKI and fibrosis. CCL28 is identified as a target of ALKBH5. Furthermore, Ccl28 mRNA stability increases with Alkbh5 deficiency, mediating by the binding of insulin-like growth factor 2 binding protein 2. Treg recruitment is upregulated and inflammatory cells are inhibited by the increased CCL28 level in IRI- Alkbh5 fl/fl Ksp Cre mice. The ALKBH5 inhibitor IOX1 exhibits protective effects against I/R-induced AKI. In summary, inhibition of ALKBH5 promotes the m6A modifications of Ccl 28 mRNA, enhancing its stability, and regulating the Treg/inflammatory cell axis. ALKBH5 and this axis is a potential AKI treatment target. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-36747-y |
| الإتاحة: | https://doi.org/10.1038/s41467-023-36747-yTest https://www.nature.com/articles/s41467-023-36747-y.pdfTest https://www.nature.com/articles/s41467-023-36747-yTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.5E303FA7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-36747-y |
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