Liang Simin, Wang Wenxuan, Gou Xin
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Mol Immunol. 2015 Jun;65(2):321-7. doi: 10.1016/j.molimm.2015.02.003. Epub 2015 Feb 28.
Ischemia-reperfusion injury (IRI) was one of the main causes of acute kidney injury. Mir-26a has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. Furthermore, the renal vein levels of Mir-26a were demonstrated to be lower in the poststenotic kidney. However, the effect of Mir-26a on the renal IRI has never been investigated. In our current study, Mir-26a overexpression results in attenuated renal IRI and promoted tregs expansion. The promoted renal function after IRI induced by Mir-26a overexpression was abrogated by depletion of tregs with anti-CD25 antibodies. Mir-26a also significantly suppressed IL-6 expression. And IL-6 overexpression led to significant suppression of the Mir-26a-induced upregulation of Foxp3. Next, we performed additional experiments to determine the therapeutic potential of Mir-26a during the recovery phase after renal IRI. Results showed that Mir-26a treatment after IRI also induced significant expansion of Foxp3(+)CD4(+) Tregs in both spleen and renal on day 10 after IRI. Taken together, our data indicate an important role for Mir-26a in promoting tregs expansion in renal IRI that involving repression of IL-6 expression.
缺血再灌注损伤（IRI）是急性肾损伤的主要原因之一。据报道，Mir-26a在细胞分化、细胞生长、细胞凋亡和转移中发挥作用。此外，狭窄后肾脏中Mir-26a的肾静脉水平较低。然而，Mir-26a对肾脏IRI的影响从未被研究过。在我们目前的研究中，Mir-26a过表达导致肾脏IRI减轻并促进调节性T细胞（Tregs）扩增。用抗CD25抗体清除Tregs可消除Mir-26a过表达诱导的IRI后肾功能的改善。Mir-26a还显著抑制白细胞介素-6（IL-6）的表达。而IL-6过表达导致Mir-26a诱导的叉头框蛋白3（Foxp3）上调受到显著抑制。接下来，我们进行了额外的实验，以确定Mir-26a在肾脏IRI后恢复阶段的治疗潜力。结果显示，IRI后第10天，Mir-26a治疗也诱导脾脏和肾脏中Foxp3(+)CD4(+) Tregs显著扩增。综上所述，我们的数据表明Mir-26a在促进肾脏IRI中Tregs扩增方面具有重要作用，这涉及抑制IL-6表达。
