间充质干细胞条件培养基通过抑制缺氧诱导因子-1α和核受体辅活化因子-1保护肾小管上皮细胞。

Chunling Liao, Yiping Liu, Yongda Lin, Jiali Wang, Tianbiao Zhou, Wenjuan Weng
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引用次数: 0

摘要

背景:急性肾损伤(AKI)以炎症浸润、肾小管上皮细胞损伤和死亡为特征,缺氧在其中起着重要作用。去甲氧胺(DFO)是一种公认的化学模拟缺氧剂。间充质干细胞条件培养基(MSC-CM)可以减少局部炎症,修复组织。在本研究中,我们探讨了MSC-CM介导的RTEC在DFO诱导的缺氧下的保护作用及其分子机制。方法:用不同浓度的DFO处理大鼠肾近端小管NRK-52E细胞24小时,然后评估RTEC损伤,使用细胞计数试剂盒-8(CCK-8)检测细胞活力,并用蛋白质印迹法评估转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA),和缺氧诱导因子-1α(HIF-1α)在NRK-52E细胞中的表达。然后,使用三组NRK-52E细胞进行实验,包括正常对照(NC)、25μM DFO和25μM DFO+MSC-CM。MSC-CM是从人脐带中获得的。在DFO处理前,使用MSC-CM培养细胞12小时,然后加入新鲜MSC-CM和25μM DFO,并在分析前再培养细胞24小时。结果:Western印迹和细胞免疫荧光染色显示,NRK-52E细胞在25μM DFO中培养24小时,诱导HIF-1α和核受体共激活因子-1(NCoA-1),模拟缺氧。MSC-CM可抑制DFO诱导的α-SMA、TGF-β1、HIF-1α和NCoA-1的上调。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mesenchymal Stem Cell-conditioned Medium Protecting Renal Tubular Epithelial Cells by Inhibiting Hypoxia-inducible Factor-1α and Nuclear Receptor Coactivator-1.

Background: Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia.

Methods: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis.

Results: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1.

Conclusion: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.

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