Hypoxic Cell-Derived Extracellular Vesicles Aggravate Rectal Injury Following Radiotherapy via MiR-122-5p.
Hypoxic Cell-Derived Extracellular Vesicles Aggravate Rectal Injury Following Radiotherapy via MiR-122-5p.
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通过 MiR-122-5p 进行放射治疗后，缺氧细胞衍生的细胞外囊泡会加重直肠损伤
DOI：
10.3389/fcell.2022.892575
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
放射性直肠损伤是放射治疗常见的副作用。放疗后常发生缺氧。本研究旨在探讨低氧对放射性直肠损伤的旁观者效应。在体内，在小鼠辐射诱导的直肠损伤模型中，直肠组织中的高度缺氧区域附近的细胞凋亡增加，表明缺氧可能参与其中。流式细胞术和Western blotting结果显示，缺氧和缺氧人肠上皮隐窝（HIEC）细胞培养上清均可促进常氧HIEC细胞凋亡。然后测定来自缺氧HIEC细胞的细胞外囊泡（EV）对常氧HIEC细胞的促凋亡作用。选择miR-122- 5 p用于通过微RNA（miRNA）微阵列测定的进一步研究，并且在接受miR-122- 5 p抑制缺氧EV的细胞中细胞凋亡减轻。总之，我们的研究表明，来源于低氧HIEC细胞的含有miR-122- 5 p的EV促进了常氧HIEC细胞的凋亡。低血压EV衍生的miR-122- 5 p在辐射诱导的直肠损伤中起关键的病理作用，并且可能是潜在的治疗靶点。
Radiation-induced rectal injury is a common side effect of radiotherapy. Hypoxia often occurs after radiotherapy. This study aimed to explore the bystander effect of hypoxia on radiation-induced rectal injury. In vivo, apoptosis increased nearby the highly hypoxic area in the rectal tissues in the mouse models of radiation-induced rectal injury, indicating the potential involvement of hypoxia. In vitro, flow cytometry and Western blotting showed that both hypoxia and hypoxic human intestinal epithelial crypt (HIEC) cell supernatant promoted apoptosis in normoxic HIEC cells. The pro-apoptotic effect of extracellular vesicles (EVs) derived from hypoxic HIEC cell to normoxic HIEC cells was then determined. MiR-122-5p was chosen for further studies through a microRNA (miRNA) microarray assay and apoptosis was alleviated in cells receiving miR-122-5p inhibiting hypoxic EVs. Together, our study demonstrated that the miR-122-5p containing-EVs derived from hypoxic HIEC cells promoted apoptosis in normoxic HIEC cells. Hypoxic EV-derived miR-122-5p plays a critical pathologic role in radiation-induced rectal injury and may be a potential therapeutic target.
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