RING finger protein 8 (RNF8) is an E3 ligase that is pivotal for DNA repair. However, the role of RNF8 in ulcerative colitis (UC) remains unclear. The aim of this study is to investigate the effect and the mechanism of RNF8 on UC model induced by trinitrobenzene sulfonic acid (TNBS) in mice. Lentiviruses overexpressing RNF8 were injected into mice after the induction of UC. The histopathologic changes in colon tissues were assessed by hematoxylin and eosin staining. The mRNA level of RNF8 was detected by qRT-PCR. The protein levels of RNF8, autophagy-related proteins (LC3 and P62) and AKT/mTOR signaling-related proteins were measured by western blot. The pro-inflammatory cytokines (TNF-α and IL-1β) were examined by immunohistochemical analysis. Immunoprecipitation was performed to analyze the interaction between RNF8 and AKT1. The TNBS-induced UC mice exhibited colonic damage and inflammation, accompanied by decreased RNF8 expression, impaired autophagy, and increased phosphorylation levels of AKT and mTOR in the colon. However, these alterations were reversed by RNF8 overexpression. Furthermore, RNF8 bound to AKT1 and mediated its ubiquitination. Collectively, RNF8 overexpression protects against TNBS-induced UC, which might be due to its enhancement of autophagy by suppressing the AKT/mTOR signaling via AKT1 ubiquitination.

中文翻译：

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RNF8通过在溃疡性结肠炎小鼠中通过泛素化促进AKT降解来诱导自噬并减少炎症。

无名指蛋白8（RNF8）是一种E3连接酶，对DNA修复至关重要。但是，RNF8在溃疡性结肠炎（UC）中的作用仍不清楚。这项研究的目的是研究三硝基苯磺酸（TNBS）诱导的小鼠肾癌中RNF8的作用及其机制。诱导UC后，将过表达RNF8的慢病毒注射入小鼠。通过苏木精和曙红染色评估结肠组织的组织病理学变化。通过qRT-PCR检测RNF8的mRNA水平。通过蛋白质印迹法测量RNF8，自噬相关蛋白（LC3和P62）和AKT / mTOR信号相关蛋白的蛋白水平。通过免疫组织化学分析检查促炎细胞因子（TNF-α和IL-1β）。进行了免疫沉淀分析RNF8和AKT1之间的相互作用。TNBS诱导的UC小鼠表现出结肠损伤和炎症，伴有RNF8表达降低，自噬受损以及结肠中AKT和mTOR的磷酸化水平升高。但是，RNF8的过量表达逆转了这些改变。此外，RNF8绑定到AKT1并介导其泛素化。总的来说，RNF8的过量表达可防御TNBS诱导的UC，这可能是由于其通过抑制经由AKT1泛素化的AKT / mTOR信号传导增强了自噬作用。