Ten-eleven translocation (Tet) methyl-cytosine dioxygenases (including Tet1/2/3)-mediated 5mC oxidation and DNA demethylation play important roles in embryonic development and adult tissue homeostasis. The expression of Tet2 and Tet3 genes are relatively abundant in the adult murine kidneys while Tet1 gene is expressed at a low level. Although Tet3 has been shown to suppress kidney fibrosis, the role of Tet2 in kidney physiology as well as renal ischemia-reperfusion (IR) injury is still largely unknown. Tet2−/− mice displayed normal kidney morphology and renal function as WT mice while the expression of genes associated with tight junction and adherens junction was impaired. At 24 h post-renal IR, Tet2−/− mice showed higher SCr and BUN levels, more severe tubular damage, and elevated expression of Kim1 and Ngal genes in the kidney in comparison with WT mice. Moreover, the transcriptomic analysis revealed augmented inflammatory response in the kidneys of Tet2−/− mice. Tet2 is dispensable for kidney development and function at baseline condition while protects against renal IR injury possibly through repressing inflammatory response. Our findings suggest that Tet2 may be a potential target for the intervention of IR-induced acute kidney injury (AKI).

中文翻译：

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10-11 易位甲基胞嘧啶双加氧酶 2 缺乏加剧肾缺血再灌注损伤。

10-11 易位 (Tet) 甲基胞嘧啶双加氧酶（包括 Tet1/2/3）介导的 5mC 氧化和 DNA 去甲基化在胚胎发育和成体组织稳态中发挥重要作用。Tet2 和 Tet3 基因在成年小鼠肾脏中的表达相对丰富，而 Tet1 基因的表达水平较低。尽管 Tet3 已被证明可以抑制肾纤维化，但 Tet2 在肾脏生理学和肾缺血再灌注 (IR) 损伤中的作用仍然很大程度上未知。Tet2-/- 小鼠表现出与 WT 小鼠一样的正常肾脏形态和肾功能，而与紧密连接和粘附连接相关的基因表达受损。在肾 IR 后 24 小时，Tet2-/- 小鼠表现出更高的 SCr 和 BUN 水平，更严重的肾小管损伤，与 WT 小鼠相比，肾脏中 Kim1 和 Ngal 基因的表达升高。此外，转录组学分析显示 Tet2-/- 小鼠肾脏炎症反应增强。Tet2 在基线条件下对于肾脏发育和功能是可有可无的，同时可能通过抑制炎症反应来防止肾脏 IR 损伤。我们的研究结果表明，Tet2 可能是干预 IR 诱导的急性肾损伤 (AKI) 的潜在目标。