Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats.
Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats.
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DOI：
10.1371/journal.pone.0202550
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kelly KJ
中科院分区：
文献类型：
--
作者：
Dominguez JM 2nd;Dominguez JH;Xie D;Kelly KJ
缺氧急性肾损伤，一个主要的未解决的问题，启动或加重肾功能和结构下降。目前尚无治疗缺氧急性肾损伤及其后遗症的方法。我们验证了裸鼠双侧肾缺血50分钟后24小时静脉输注人肾小管细胞或其细胞外囊泡（外泌体）可以预防肾损伤的假设。细胞和它们的外泌体来自摘取的人类肾脏，谢绝移植。在再灌注24小时和48小时后注射细胞或外泌体，两组患者的肾脏功能和结构均得以保存。然而，外泌体优于细胞；维持肾脏血管和上皮网络，防止肾脏氧化应激和细胞凋亡；抑制促炎和促纤维化途径的激活。外泌体在24小时内起作用，符合功能性而非再生活性。综合蛋白质组学分析从所有细胞区室中鉴定出6152个肾脏蛋白；628只小鼠在各细胞水平均出现缺血改变，377只小鼠外泌体输注后明显改善。我们得出结论，严重缺血对肾脏的损害是广泛的，人类肾外泌体阻止了大多数蛋白质的改变。因此，外泌体似乎能在再灌注过程中敏锐地纠正一个关键的和相应的异常。在缺乏它们的情况下，肾脏结构和细胞转变为慢性纤维化状态和广泛的肾细胞损失。
Hypoxic acute kidney injury, a major unresolved problem, initiates, or aggravates, renal functional and structural decline. There is no treatment for hypoxic acute renal injury and its sequelae. We tested the hypothesis that human kidney tubular cells, or their extracellular vesicles (exosomes), prevent renal injury when infused intravenously 24 hours after 50 minutes of bilateral renal ischemia in Nude rats. Cells and their exosomes were from harvested human kidneys declined for transplantation. Injections of either cells or exosomes, given after 24 and 48 hours of reperfusion, preserved renal function and structure in both treatment groups. However, exosomes were superior to cells; and maintained renal vascular and epithelial networks, prevented renal oxidant stress, and apoptosis; and restrained activation of pro-inflammatory and pro-fibrogenic pathways. Exosomes worked in 24 hours, consistent with functional rather than regenerative activity. Comprehensive proteomic analysis identified 6152 renal proteins from all cellular compartments; and 628 were altered by ischemia at all cell levels, while 377 were significantly improved by exosome infusions. We conclude that renal damage from severe ischemia was broad, and human renal exosomes prevented most protein alterations. Thus, exosomes seem to acutely correct a critical and consequential abnormality during reperfusion. In their absence, renal structure and cells transition to a chronic state of fibrosis and extensive renal cell loss.
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影响因子：
3.7
作者：
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13.6
作者：
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