Metal–organic frameworks induce autophagy in mouse embryonic fibroblast cells
Metal–organic frameworks induce autophagy in mouse embryonic fibroblast cells
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金属有机框架诱导小鼠胚胎成纤维细胞自噬
DOI：
10.1039/c8nr04459g
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发表时间：
2018
期刊：
影响因子：
6.7
通讯作者：
Huwei Liu
中科院分区：
文献类型：
--
作者：
Sensen Shen;Linnan Li;Songyue Li;Yu Bai;Huwei Liu
自噬是细胞内物质适应环境或发育变化的溶酶体依赖性降解过程。它在维持细胞内稳态中起着重要作用，而其功能障碍与各种人类疾病有关。自噬的调节引起了越来越多的关注，并有望作为潜在的治疗靶点改善疾病的治疗。金属有机骨架材料作为一种新兴的生物材料，近年来在生物医学领域得到了广泛的研究。因此，从安全性和治疗角度研究MOFs对活细胞的影响，特别是它们对自噬的影响，是有趣和有意义的，尚未报道。本研究探讨了Fe-MIL-101_NH2对小鼠胚胎成纤维细胞（MEFs）的作用，并探讨了其在自噬调控中的潜在应用。我们的结果表明，Fe-MIL-101_NH2诱导MEFs的细胞保护性自噬，而不是细胞毒性。自噬的激活阻止了活性氧的积累，从而保护了MEFs免于凋亡。对MOF诱导自噬的可能机制的进一步探讨表明，mTOR通路的抑制以及Becline 1和Atg 5的增强有助于自噬的诱导。本研究揭示了MOFs的自噬作用及其机制，对MOFs的安全性评价和合理有效使用具有重要意义。
Autophagy is the lysosomal-dependent degradation process of intracellular substances in adaptation to environmental or developmental changes. It plays an essential role in maintaining cellular homeostasis while its dysfunction is involved in various human diseases. The regulation of autophagy has attracted more and more attention with the promise for improving treatment of diseases as a potential therapeutic target. Metal–organic frameworks (MOFs), as emerging biomaterials, have been investigated in the biological and biomedical fields in recent years. Therefore, it is interesting and significant to study the effects of MOFs on living cells from safety aspects as well as the therapeutic viewpoint, especially their effects on autophagy which have not been reported yet. In this study, the effects of Fe-MIL-101_NH2 on mouse embryonic fibroblasts (MEFs) were investigated and the potential applications of these nanoparticles in the regulation of autophagy were explored. Our results demonstrated that Fe-MIL-101_NH2 induced cytoprotective autophagy in MEFs instead of cytotoxicity. The activation of autophagy kept reactive oxygen species from accumulating, which protected MEFs from apoptosis. Further exploration of the possible mechanisms of MOF-induced autophagy revealed that the inhibition of mTOR pathway as well as the enhancement of Becline1 and Atg5 contributed to autophagy induction. Our study uncovered the autophagic effects and mechanistic insights of MOFs, which will be beneficial and meaningful to the safety evaluation and the reasonable and effective usage of MOFs.