miR-17-5p attenuates kidney ischemia-reperfusion injury by inhibiting the PTEN and BIM pathways.
miR-17-5p attenuates kidney ischemia-reperfusion injury by inhibiting the PTEN and BIM pathways.
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miR-17-5p通过抑制PTEN和BIM途径减轻肾脏缺血再灌注损伤
DOI：
10.21037/atm-21-4678
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发表时间：
2021-10
影响因子：
--
通讯作者：
Song T
中科院分区：
文献类型：
--
作者：
Ma M;Fu L;Jia Z;Zhong Q;Huang Z;Wang X;Fan Y;Lin T;Song T
肾缺血再灌注（I/R）损伤是肾移植术后移植肾功能延迟恢复和移植肾长期存活恶化的独立危险因素。先前我们发现miR-17- 5 p表达上调对肾I/R损伤具有保护作用，但其机制尚不清楚。在成年C57 BL/6雄性小鼠（20-22 g）中通过夹闭两个肾蒂30 min诱导肾I/R损伤模型。在手术前24 h通过尾静脉将miR-17- 5 p阿戈米尔复合物注射到小鼠体内，总注射体积为10 µL/g体重。在I/R损伤后第2天处死小鼠，然后检测肾功能、细胞凋亡、自噬和相关分子。用miR-17- 5 p阿戈米尔、miR-17- 5 p阿托米尔和小干扰核糖核酸（siRNA）处理经历缺氧/复氧的人肾-2（HK-2）细胞。还检查了细胞活力、凋亡、自噬和分子。自噬、miR-17- 5 p表达和肾功能损害在I/R组比假手术组显著增加。在缺氧/复氧培养的HK-2细胞中，miR-17- 5 p agomir可直接抑制10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）和Bcl-2样蛋白11（BIM）的表达，减少细胞凋亡和自噬。此外，miR-17- 5 p通过激活蛋白激酶B（Akt）/Beclin 1途径抑制自噬，该途径被siRNA抑制。此外，miR-17- 5 p agomir的给药通过抑制自噬和凋亡大大改善了I/R小鼠组的肾功能。这些发现为预防和治疗肾I/R损伤提供了一种新的可能的治疗策略。miR-17- 5 p表达的上调似乎通过抑制PTEN和BIM表达来抑制细胞凋亡和自噬，这反过来又上调下游Akt/Beclin 1表达。
Kidney ischemia-reperfusion (I/R) injury is an independent risk factor for delayed graft function after kidney transplantation with long-term graft survival deterioration. Previously, we found that the upregulated expression of miR-17-5p exerts a protective effect in kidney I/R injury, but the mechanism has not been clearly studied. A kidney I/R injury model was induced in adult C57BL/6 male mice (20–22 g) by clamping both kidney pedicles for 30 min. The miR-17-5p agomir complex was injected into mice 24 h before surgery via the tail vein at a total injection volume of 10 µL/g body weight. The mice were euthanized on post-I/R injury day 2, and kidney function, apoptosis, autophagy, and related molecules were then detected. Human kidney-2 (HK-2) cells, which underwent hypoxia/reoxygenation, were treated with the miR-17-5p agomir, miR-17-5p antagomir, and small interfering ribonucleic acids (siRNAs). Cell viability, apoptosis, autophagy, and molecules were also examined. Autophagy, miR-17-5p expression, and kidney function damage were significantly more increased in the I/R group than in the sham group. In the cultured HK-2 cells underwent hypoxia/reoxygenation, the miR-17-5p agomir directly inhibited the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Bcl-2 like protein 11 (BIM), and attenuated apoptosis and autophagy. Further, miR-17-5p inhibited autophagy by activating the protein kinase B (Akt)/Beclin1 pathway, which was suppressed by siRNAs. Additionally, the administration of miR-17-5p agomir greatly improved kidney function in the I/R mice group by inhibiting autophagy and apoptosis. These findings suggest a new possible therapeutic strategy for the prevention and treatment of kidney I/R injury. The upregulation of miR-17-5p expression appears to inhibit apoptosis and autophagy by suppressing PTEN and BIM expression, which in turn upregulates downstream Akt/Beclin1 expression.
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