Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
Environ Toxicol. 2023 Jul;38(7):1732-1742. doi: 10.1002/tox.23801. Epub 2023 Apr 4.
Preliminary researches have confirmed that the number of apoptosis of adipose tissue-derived stem cells (ADSCs) in patients with diabetes is significantly increased, leading to a difficult healing wound. Increasing researches revealed that circular RNAs (circRNAs) can control apoptosis. However, it is still unclear whether and how circRNAs are critical for regulating ADSCs apoptosis. In this study, we utilized in vitro model in which ADSCs were cultivated with normal glucose (NG) (5.5 mM) or high glucose (HG) (25 mM) medium, respectively, and found that more apoptotic ADSCs were observed in HG medium comparing to ADSCs in NG medium. Furthermore, we found that hsa_circ_0008500 attenuated HG-mediated ADSCs apoptosis. In addition, Hsa_circ_0008500 could directly interact with hsa-miR-1273h-5p, acting as a miRNA sponge, which subsequently suppressed Ets-like protein-1(ELK1) expression, the downstream target of hsa-miR-1273h-5p. Thus, these results indicated that targeting the hsa_circ_0008500/hsa-miR-1273h-5p/ELK1 signaling pathway in ADSCs may be a potential target for repairing diabetic wounds.
初步研究证实，糖尿病患者脂肪组织来源的干细胞（ADSCs）的凋亡数量明显增加，导致伤口难以愈合。越来越多的研究表明，环状 RNA（circRNA）可以控制细胞凋亡。然而，circRNA 是否以及如何对调节 ADSCs 凋亡起关键作用仍不清楚。在本研究中，我们利用体外模型，分别将 ADSCs 在正常葡萄糖（NG）（5.5mM）或高葡萄糖（HG）（25mM）培养基中培养，发现 HG 培养基中的 ADSCs 凋亡数量明显高于 NG 培养基中的 ADSCs。此外，我们发现 hsa_circ_0008500 可以减弱 HG 介导的 ADSCs 凋亡。此外，hsa_circ_0008500 可以直接与 hsa-miR-1273h-5p 相互作用，作为 miRNA 海绵，从而抑制 hsa-miR-1273h-5p 的下游靶基因 Ets 样蛋白-1（ELK1）的表达。因此，这些结果表明，靶向 ADSCs 中的 hsa_circ_0008500/hsa-miR-1273h-5p/ELK1 信号通路可能是修复糖尿病创面的潜在靶点。
