Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Doctor's Office, 10th floor, building 2, NO.507 Zhengmin Road, Yangpu District, Shanghai, 200433, P.R. China.
Mol Cell Biochem. 2021 Oct;476(10):3745-3756. doi: 10.1007/s11010-021-04170-w. Epub 2021 Jun 7.
Sepsis is one of the leading causes of morbidity and mortality and a major cause of acute lung injury (ALI). carried by exosomes play a role in a variety of diseases. However,there are not many studies of exosomal miRNAs in sepsis and sepsis lung injury.miR-1298-5p and suppressor of cytokine signaling 6 (SOCS6) were silenced or overexpressed in human bronchial epithelial cells (BEAS-2B). PKH-67 Dye was used to trace exosome endocytosis. Cell permeability was evaluated by measuring trans-epithelial electrical resistance (TEER) and FITC dextran flux. ELISA kits were used for cytokine detection. Quantitative RT-PCR and western blots were used to evaluate gene expression. miR-1298-5p was elevated in exosomes from patients with sepsis lung injury (Sepsis_exo). Treatment of BEAS-2B cells using Sepsis_exo significantly inhibited cell proliferation, and induced cell permeability and inflammatory response. miR-1298-5p directly targeted SOCS6. Overexpressing SOCS6 reversed miR-1298-5p-induced cell permeability and inflammatory response. Inhibition of STAT3 blocked SOCS6-silencing caused significant increase of cell permeability and inflammation. Exosomes isolated from patients of sepsis lung injury increased cell permeability and inflammatory response in BEAS-2B cells through exosomal miR-1298-5p which targeted SOCS6 via STAT3 pathway. The findings highlight the importance of miR-1298-5p/SOCS6/STAT3 axis in sepsis lung injury and provide new insights into therapeutic strategies for sepsis lung injury.
脓毒症是发病率和死亡率的主要原因之一，也是急性肺损伤（ALI）的主要原因。外泌体所携带的 miRNA 在各种疾病中发挥作用。然而，关于脓毒症和脓毒症肺损伤中外泌体 miRNA 的研究并不多。在人支气管上皮细胞（BEAS-2B）中沉默或过表达 miR-1298-5p 和细胞因子信号转导抑制因子 6（SOCS6）。使用 PKH-67 染料追踪外泌体的内吞作用。通过测量跨上皮电阻（TEER）和 FITC 葡聚糖通量来评估细胞通透性。使用 ELISA 试剂盒检测细胞因子。采用定量 RT-PCR 和 Western blot 检测基因表达。脓毒症肺损伤患者来源的外泌体中 miR-1298-5p 水平升高（Sepsis_exo）。用 Sepsis_exo 处理 BEAS-2B 细胞可显著抑制细胞增殖，并诱导细胞通透性和炎症反应。miR-1298-5p 可直接靶向 SOCS6。过表达 SOCS6 逆转了 miR-1298-5p 诱导的细胞通透性和炎症反应。抑制 STAT3 阻断了 SOCS6 沉默引起的细胞通透性和炎症的显著增加。脓毒症肺损伤患者分离的外泌体通过外泌体 miR-1298-5p 靶向 SOCS6 通过 STAT3 通路增加 BEAS-2B 细胞的细胞通透性和炎症反应。这些发现强调了 miR-1298-5p/SOCS6/STAT3 轴在脓毒症肺损伤中的重要性，并为脓毒症肺损伤的治疗策略提供了新的思路。
