Li Chen, Liu Jianhua, Feng Gaixia, Su Jing, Xu Kailun, Zhang Zhihua
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, No. 12 Changqing Road, Qiaoxi District, Zhangjiakou, 075000, Hebei, China.
J Mol Histol. 2025 May 26;56(3):168. doi: 10.1007/s10735-025-10465-9.
Acute lung injury (ALI) induced by sepsis is a serious life-threatening disease, one of its characteristics is the polarization of macrophages. Circ_0008285 has been found to be associated with various diseases. In this study, we detected the regulatory role and mechanism of circ_0008285 in sepsis-induced ALI. RAW264.7 cells treated with LPS and C57BL/6 male mice were used to construct in vitro and in vivo models, respectively. Through A series of experiments such as qRT-PCR, Western blot, CCK-8, flow cytometry, dual-luciferase reporter experiment, HE staining and TUNEL staining, the role of circ_0008285 in sepsis-induced ALI was explored. In LPS-induced RAW264.7 cell, circ_0008285 and MAPK14 were over-expressed, but miR-375 was low-expressed compared with control. The levels of IL-1β, IL-6, TNF-α, iNOS and CD86 were reduced, but CD206 and Arg1 expression were enhanced both in vitro and in vivo after knockdown of circ_0008285. In TC-1 cell co-cultured with LPS+sh-circ_0008285 cells, the viability was increased and the apoptosis level was decreased compared with LPS+sh-NC. Circ_0008285 was the sponge of miR-375, and MAPK14 was the downstream target of miR-375. The injury score, W/D ratio, MPO level and apoptosis level in lung tissue were decreased after knockdown of circ_0008285. Moreover, the total protein, neutrophils and macrophages in BALF were increased. Collectively, this study identified that circ_0008285 could sponge miR-375 to influence MAPK14 expression, and then regulate macrophage polarization of sepsis-induced ALI, which provided new insights for the treatment of sepsis-induced ALI.
脓毒症诱导的急性肺损伤（ALI）是一种严重威胁生命的疾病，其特征之一是巨噬细胞极化。已发现Circ_0008285与多种疾病相关。在本研究中，我们检测了Circ_0008285在脓毒症诱导的ALI中的调控作用及机制。分别用LPS处理的RAW264.7细胞和C57BL/6雄性小鼠构建体外和体内模型。通过qRT-PCR、蛋白质免疫印迹、CCK-8、流式细胞术、双荧光素酶报告基因实验、HE染色和TUNEL染色等一系列实验，探讨了Circ_0008285在脓毒症诱导的ALI中的作用。在LPS诱导的RAW264.7细胞中，与对照组相比，Circ_0008285和MAPK14过表达，但miR-375低表达。敲低Circ_0008285后，体外和体内IL-1β、IL-6、TNF-α、iNOS和CD86水平降低，但CD206和Arg1表达增强。在与LPS+sh-Circ_0008285细胞共培养的TC-1细胞中，与LPS+sh-NC相比，细胞活力增加，凋亡水平降低。Circ_0008285是miR-375的海绵，MAPK14是miR-375的下游靶点。敲低Circ_0008285后，肺组织损伤评分、湿干比、MPO水平和凋亡水平降低。此外，BALF中的总蛋白、中性粒细胞和巨噬细胞增加。总的来说，本研究发现Circ_0008285可以吸附miR-375以影响MAPK14表达，进而调节脓毒症诱导的ALI的巨噬细胞极化，为脓毒症诱导的ALI的治疗提供了新的见解。
