Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury.
Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury.
复制标题
人脐带衍生的间充质基质细胞可预防急性肾损伤大鼠氧化应激引起的过早肾脏衰老。
DOI：
10.1186/s13287-017-0475-8
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发表时间：
2017-01-28
影响因子：
7.5
通讯作者：
Andrade L
中科院分区：
文献类型：
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作者：
Rodrigues CE;Capcha JM;de Bragança AC;Sanches TR;Gouveia PQ;de Oliveira PA;Malheiros DM;Volpini RA;Santinho MA;Santana BA;Calado RD;Noronha IL;Andrade L
间充质间质细胞（MSCs）是治疗急性肾损伤（AKI）的一种选择。众所周知，在减少肾脏衰老表型的发生率方面，年轻的干细胞比年老的干细胞更好。本研究的目的是确定AKI是否会导致应力诱导的过早衰老，以及人脐带源性间充质干细胞（huMSCs）是否可以预防缺血/再灌注损伤（IRI）诱导的大鼠肾衰老。通过夹持双肾动脉45分钟，我们诱导了雄性大鼠的IRI。6小时后，部分大鼠腹腔注射1 × 106个huMSCs或人脂肪来源的MSCs （aMSCs）。对大鼠实施安乐死，并在iri后第2、7和49天进行研究。在iri后第2天，humsc处理的大鼠肾脏肾小球滤过改善，小管功能改善，水通道蛋白2表达增加，巨噬细胞浸润减少。衰老相关蛋白（β-半乳糖苷酶、p21Waf1/Cip1、p16INK4a和转化生长因子β 1）和microrna （miR-29a和miR-34a）在IRI后过表达，随后被处理下调。iri诱导的促氧化状态和Klotho表达的降低均被治疗逆转。与huMSC治疗相比，aMSCs治疗对肾功能的改善程度较低，肾脏Klotho和锰超氧化物歧化酶表达的增加也不太明显。huMSCs治疗可改善IRI后的长期肾功能，减少肾纤维化，降低β-半乳糖苷酶表达，增加Klotho表达。我们的数据表明，huMSCs可以减轻AKI中发生的炎症和氧化应激反应，并降低衰老相关蛋白和microrna的表达。我们的发现拓宽了AKI治疗的视角。本文的在线版本（doi:10.1186/s13287-017-0475-8）包含补充材料，可供授权用户使用。
Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats. By clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 × 106 huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49. On post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (β-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) and microRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased β-galactosidase expression and increased the expression of Klotho. Our data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI. The online version of this article (doi:10.1186/s13287-017-0475-8) contains supplementary material, which is available to authorized users.