Mitochondria transfer via tunneling nanotubes is an important mechanism by which CD133+ scattered tubular cells eliminate hypoxic tubular cell injury
Mitochondria transfer via tunneling nanotubes is an important mechanism by which CD133+ scattered tubular cells eliminate hypoxic tubular cell injury
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通过隧道纳米管进行线粒体转移是CD133分散的肾小管细胞消除缺氧肾小管细胞损伤的重要机制
DOI：
10.1016/j.bbrc.2019.11.006
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sun Jie
中科院分区：
文献类型：
--
作者：
Zou Xiangyu;Hou Yanping;Xu Jinxia;Zhong Liang;Zhou Jin;Zhang Guangyuan;Sun Jie
肾CD133 +散在小管细胞（STCs）被认为是肾脏的祖细胞样细胞，参与了缺血性肾损伤的修复。然而，这种作用的机制尚未完全阐明。本研究的主要目的是研究CD133 + STCs的保护作用取决于线粒体向体外受损小管细胞的转移这一假设。本研究建立肾缺血再灌注损伤（IRI）大鼠模型，单侧肾缺血45 min，术后48 h处死。分离体外培养小管细胞，从培养细胞中筛选CD133 + STCs。然后，将CD133 + STCs与CD133-小管细胞（tec）共培养，检测其隧穿纳米管样结构，并通过荧光成像和流式细胞术检测CD133 + STCs向损伤小管细胞的线粒体转移。此外，在缺氧条件下，CD133 + STCs与tec一起培养，测试了其细胞保护作用。结果：肾CD133 + STCs分散分布于正常肾脏，并在缺血损伤时增加。CD133 + STCs和tec之间普遍存在纳米管形成，并且检测到线粒体从CD133 + STCs向tec的转移。此外，在缺氧培养条件下，CD133 + STCs对tec具有显著的抗凋亡和促增殖作用。因此，本研究首次描述了肾脏CD133 + STCs可以将线粒体转移到体外损伤的TECsin中并发挥其保护作用，揭示了缺血性损伤后肾脏修复的重要新机制。
AbstractsRenal CD133 + scattered tubular cells (STCs) have been regarded as progenitor-like cells in the kidney and participated in ischemic renal injury repair. However, the mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the protective effect of CD133 + STCs depends on the transfer of mitochondria to injured tubular cellsin vitro. In this study, renal ischemic reperfusion injury (IRI) rat model was established with one side kidney ischemic for 45 min and animals were sacrificed at 48 h after operation. Tubular cells were isolated and culturedin vitro, and then CD133 + STCs were selected from the cultured cells. Then, CD133 + STCs were co-cultured with CD133-tubular cells (TECs) to detect the tunneling nanotubes like structures, and the transfer of mitochondria from CD133 + STCs to injured tubular cells were detected by fluorescent imaging and flow cytometry. Further, cellular protective effects of CD133 + STCs were tested when cultured with TECs under hypoxic conditions. In results, renal CD133 + STCs were scattered throughout the normal kidney and increased upon ischemic injury. Nanotube formations were commonly found between CD133 + STCs and TECs, and the transfer of mitochondria was detected from CD133 + STCs to TECs. Further, CD133 + STCs exist significant anti-apoptosis and pro-proliferation effects for TECs under hypoxic culture conditions. Thus, this study was first described that renal CD133 + STCs could transfer mitochondria to injured TECsin vitrofor its protective effects, which revealed an important novel mechanism for renal repair after ischemic injury.