Department of Emergency Medicine, Lishui Second People's Hospital, No. 69, North Ring Road, Liandu District, Lishui City, 323000, Zhejiang Province, China.
J Bioenerg Biomembr. 2023 Aug;55(4):301-312. doi: 10.1007/s10863-023-09978-3. Epub 2023 Aug 5.
Sepsis is a systemic inflammatory disease that can cause a variety of diseases, including septic acute kidney injury (AKI). Circular RNAs (circRNAs) are believed to be involved in the development of this disease. This study aims to clarify the function of circ_0001806 in lipopolysaccharide (LPS)-induced HK2 cell model and its related mechanisms. Circ_0001806 was up-regulated in septic AKI serum specimens and LPS-induced HK2 cells. Circ_0001806 knockdown promoted cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In mechanism, circ_0001806 can be used as a sponge for miR-942-5p, and miR-942-5p can directly target TXNIP. Functional experiments revealed that the miR-942-5p inhibitor could reverse the alleviating effect of circ_0001806 knockdown on LPS-induced HK2 cell injury, and TXNIP addition can also reverse the inhibitory effect of miR-942-5p overexpression on LPS-induced HK2 cell injury. In addition, circ_0001806 regulated TXNIP expression through sponging miR-942-5p. Besides, exosome-derived circ_0001806 was upregulated in LPS-induced HK2 cells, while was downregulated by GW4869. The results showed that circ_0001806 knockdown could reduce LPS-induced HK2 cell injury by regulating TXNIP expression via targeting miR-942-5p, indicating that circ_0001806 might be an important biomarker for alleviating sepsis-related AKI. This might provide therapeutic strategy for the treatment of sepsis.
脓毒症是一种全身性炎症性疾病,可引起多种疾病,包括脓毒性急性肾损伤(AKI)。环状 RNA(circRNA)被认为参与了这种疾病的发展。本研究旨在阐明 circ_0001806 在脂多糖(LPS)诱导的 HK2 细胞模型中的功能及其相关机制。circ_0001806 在脓毒症 AKI 血清标本和 LPS 诱导的 HK2 细胞中上调。circ_0001806 敲低促进 LPS 诱导的 HK2 细胞增殖,抑制细胞凋亡、炎症和氧化应激。在机制上,circ_0001806 可以作为 miR-942-5p 的海绵,而 miR-942-5p 可以直接靶向 TXNIP。功能实验表明,miR-942-5p 抑制剂可以逆转 circ_0001806 敲低对 LPS 诱导的 HK2 细胞损伤的缓解作用,而 TXNIP 加回也可以逆转 miR-942-5p 过表达对 LPS 诱导的 HK2 细胞损伤的抑制作用。此外,circ_0001806 通过海绵吸附 miR-942-5p 调节 TXNIP 表达。此外,外泌体来源的 circ_0001806 在 LPS 诱导的 HK2 细胞中上调,而被 GW4869 下调。结果表明,circ_0001806 敲低通过靶向 miR-942-5p 调节 TXNIP 表达可减轻 LPS 诱导的 HK2 细胞损伤,表明 circ_0001806 可能是缓解脓毒症相关 AKI 的重要生物标志物。这可能为脓毒症的治疗提供了一种治疗策略。