miR-127 protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3B as miR-127 target.
miR-127 protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3B as miR-127 target.
复制标题
DOI：
10.1371/journal.pone.0044305
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bermejo ML
中科院分区：
文献类型：
--
作者：
Aguado-Fraile E;Ramos E;Sáenz-Morales D;Conde E;Blanco-Sánchez I;Stamatakis K;del Peso L;Cuppen E;Brüne B;Bermejo ML
缺血再灌注（Ischemia/reperfusion, I/R）是肾移植和急性肾损伤的基础。近端小管对I/R反应的分子机制将为两种临床环境确定新的治疗靶点。microRNAs已经成为细胞对包括缺氧在内的损伤反应的关键和严格的调节剂。在这里，我们已经确定了几个mirna参与近端小管细胞对I/R的反应。体外I/R模拟条件下近端小管细胞的微阵列和RT-PCR分析表明，miR-127在缺血和再灌注过程中被诱导。miR-127在肾I/R大鼠模型中也受到调节。干扰方法表明miR-127的缺血诱导是由缺氧诱导因子-1α (HIF-1α)稳定介导的。此外，miR-127参与细胞-基质和细胞-细胞粘附的维持，因为miR-127的过表达维持了局灶粘附复合物的组装和紧密连接的完整性。miR-127也调节细胞内运输，因为miR-127的干扰促进右旋糖酐- fitc的摄取。事实上，我们已经确定参与细胞运输的Kinesin家族成员3B （KIF3B）是大鼠近端小管细胞中miR-127的靶标。总之，我们已经描述了miR-127在细胞粘附及其HIF-1α调控中的新作用。我们还首次发现KIF3B是miR-127的靶点。miR-127和KIF3B似乎都是近端上皮小管细胞对I/R反应的关键介质，在肾缺血损伤管理中具有潜在的应用价值。
Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia. Here, we have identified several miRNAs involved in the response of the proximal tubule cell to I/R. Microarrays and RT-PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in vitro demonstrated that miR-127 is induced during ischemia and also during reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia Inducible Factor-1alpha (HIF-1α) stabilization. Moreover, miR-127 is involved in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR-127 maintains focal adhesion complex assembly and the integrity of tight junctions. miR-127 also regulates intracellular trafficking since miR-127 interference promotes dextran-FITC uptake. In fact, we have identified the Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of miR-127 in rat proximal tubule cells. In summary, we have described a novel role of miR-127 in cell adhesion and its regulation by HIF-1α. We also identified for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as key mediators of proximal epithelial tubule cell response to I/R with potential al application in renal ischemic damage management.
登录
查看更多内容
影响因子：
3.7
作者：
Conde E;Alegre L;Blanco-Sánchez I;Sáenz-Morales D;Aguado-Fraile E;Ponte B;Ramos E;Sáiz A;Jiménez C;Ordoñez A;López-Cabrera M;del Peso L;de Landázuri MO;Liaño F;Selgas R;Sanchez-Tomero JA;García-Bermejo ML
通讯作者：
García-Bermejo ML
影响因子：
4.4
作者：
Linsen SE;de Wit E;de Bruijn E;Cuppen E
通讯作者：
Cuppen E
影响因子：
6.4
作者：
Leucci, Eleonora;Onnis, Anna;Leoncini, Lorenzo
通讯作者：
Leoncini, Lorenzo
DOI：
10.1159/000313738
发表时间：
2010-01-01
期刊：
CARDIORENAL SYNDROMES IN CRITICAL CARE
影响因子：
--
作者：
Bonventre, Joseph V.
通讯作者：
Bonventre, Joseph V.
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.