Influence of erythropoietin on microvesicles derived from mesenchymal stem cells protecting renal function of chronic kidney disease.
Influence of erythropoietin on microvesicles derived from mesenchymal stem cells protecting renal function of chronic kidney disease.
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促红细胞生成素对间充质干细胞微泡保护慢性肾病肾功能的影响。
DOI：
10.1186/s13287-015-0095-0
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发表时间：
2015-05-22
影响因子：
7.5
通讯作者：
Zhao W
中科院分区：
文献类型：
--
作者：
Wang Y;Lu X;He J;Zhao W
间充质干细胞（MSCs）在细胞和组织损伤的修复中起着核心作用。促红细胞生成素（EPO）可以增强MSC在组织和器官损伤恢复过程中的有益影响。从MSC释放的微囊泡（MV）有助于肾损伤的恢复。我们研究了促红细胞生成素对骨髓间充质干细胞来源的微血管的影响，以及这些因素对慢性肾脏病（CKD）受试者的保护作用。用未处理的MSC（MSC-MVs）或不同浓度EPO（1、10、100和500 IU/ml）孵育的MSC（MSC-MVs）治疗单侧输尿管梗阻（UUO）所致的肾损伤和转化生长因子-β1（TGF-β1）诱导的人近端肾小管上皮细胞（HK 2）纤维化。Western blot和逆转录聚合酶链反应（RT-PCR）检测肾组织和HK 2细胞中上皮和间充质标志物的表达。流式细胞术用于评估HK 2细胞内的凋亡，并且microRNA（miRNA）微阵列分析用于确定MSC-MV和EPO-MV中miRNA的表达谱。与MSC-MV（未处理）相比，用1-100 IU/ml EPO处理的MSC衍生的EPO-MV的数量显著增加，并且这些EPO-MV在第7天和第14天在UUO小鼠中具有更大的益处。EPO-MVs对TGF-β1诱导的HK 2细胞纤维化在24 h和48 h有较好的修复作用。流式细胞仪检测结果显示，两种MVs，尤其是EPO-MVs，在TGF-β1处理的HK 2细胞中均发挥了重要的抗凋亡作用。MV的miRNA谱显示，EPO-MV改变了212种miRNA（倍数变化≥ 1.5），包括miR-299、miR-499、miR-302和miRNA-200，其中70.28%的变化涉及上调。与MSC-MV相比，EPO-MV中改变的miRNA可能有助于增强其在肾损伤后的保护作用。在1-100 IU/ml EPO范围内，EPO-MV水平呈剂量依赖性增加。尽管MSC-MV和EPO-MV都能保护肾脏免受纤维化相关损伤，但EPO-MV的效果上级。本文的在线版本（doi：10.1186/s13287-015-0095-0）包含补充材料，可供授权用户使用。
Mesenchymal stem cells (MSCs) play a central role in the remediation of cell and tissue damage. Erythropoietin (EPO) may enhance the beneficial influence of MSCs during recovery from tissue and organ injuries. Microvesicles (MVs) released from MSCs contribute to the restoration of kidney damage. We studied the influence of EPO on MVs derived from MSCs, and the protective effects of these factors in subjects with chronic kidney disease (CKD). The MVs derived from untreated MSCs (MSC-MVs) or from MSCs incubated in different concentrations of EPO (1, 10, 100, and 500 IU/ml EPO-MVs) were used to treat renal injury of unilateral ureteral obstruction (UUO) in vivo, and transforming growth factor-β1 (TGF-β1)-induced fibrosis in a human renal proximal tubular epithelial (HK2) cell line in vitro. Western blot and reverse transcription polymerase chain reaction (RT-PCR) analyses were used to evaluate the expression of epithelial and mesenchymal markers in the renal tissue and HK2 cells. Flow cytometry was used to assess apoptosis within the HK2 cells, and microRNA (miRNA) microarray assays were used to determine the expression profiles of miRNA in the MSC-MVs and EPO-MVs. Compared to MSC-MVs (untreated), there was a significant increase in the number of EPO-MVs derived from MSCs treated with 1–100 IU/ml EPO, and these EPO-MVs had a greater benefit in UUO mice on days 7 and 14. Moreover, the EPO-MVs had a better restorative effect following TGF-β1-induced fibrosis in HK2 cells at 24 h and 48 h. The flow cytometry results revealed that both types of MVs, especially EPO-MVs, play an important anti-apoptotic role in HK2 cells treated with TGF-β1. The miRNA profiles of the MVs revealed that EPO-MVs changed 212 miRNAs (fold-change ≥ 1.5), including miR-299, miR-499, miR-302, and miRNA-200, and that 70.28 % of these changes involved upregulation. The changed miRNA in EPO-MVs may have contributed to their enhanced protective effects following renal injury compared to MSC-MVs. There was a dose-dependent increase in the level of EPO-MVs within the range of 1–100 IU/ml EPO. Although both MSC-MVs and EPO-MVs protect the kidney from fibrosis-related damage, there is a superior effect of EPO-MVs. The online version of this article (doi:10.1186/s13287-015-0095-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
3.7
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
3.3
作者：
Magnasco, Alberto;Corselli, Mirko;Ghiggeri, Gian Marco
通讯作者：
Ghiggeri, Gian Marco