Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma.

Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma.
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DOI:
10.4103/1673-5374.224382
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发表时间:
2018-01
影响因子:
6.1
通讯作者:
Niknazar S
Niknazar S
中科院分区:
医学2区
文献类型:
--
作者:
Peyvandi AA;Roozbahany NA;Peyvandi H;Abbaszadeh HA;Majdinasab N;Faridan M;Niknazar S

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先前的动物研究表明,基质细胞衍生因子-1 (SDF-1)/CXC趋化因子受体-4 (CXCR4)信号通路在骨髓间充质干细胞(BMSCs)向损伤区域的靶向迁移中起重要作用。在本研究中,我们旨在探讨趋化性SDF-1/CXCR4信号通路在大鼠噪声性听力损失(NIHL)后移植的骨髓间充质干细胞归巢到受损耳蜗中的潜在作用。采用白噪声(110 dB)模式诱导雄性大鼠听力损失,实验时间为5天6小时。在实验前和噪声暴露后记录畸变积耳声发射(DPOAE)响应。将Hoechst 33342标记的骨髓间充质干细胞和CXCR4拮抗剂(AMD3100)处理的骨髓间充质干细胞通过圆窗注入大鼠耳蜗。western blot法检测耳蜗组织中SDF-1蛋白的表达。24小时后检测到达内淋巴的标记骨髓间充质干细胞数量。噪声暴露组大鼠耳蜗组织中SDF-1明显高于对照组。amd3100处理组到达耳蜗内淋巴的Hoechst 33342标记的骨髓间充质干细胞数量明显少于正常骨髓间充质干细胞组。我们目前的研究结果表明,在噪声性听力损失大鼠模型中,SDF-1/CXCR4信号通路在骨髓间充质干细胞向受损耳蜗的迁移中起关键作用。
Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure. Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours. SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss.
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