Li Jing, Wu Jing, Zhao Lili, Liu Lian
Department of Neonatology, Chongqing Bishan District Maternal and Child Health Hospital, Chongqing, China.
Department of Pediatrics, University-Town Hospital of Chongqing Medical University, Chongqing, China.
Clin Respir J. 2025 May;19(5):e70079. doi: 10.1111/crj.70079.
Intercellular cell adhesion molecule 1 (ICAM1) has been confirmed to be abnormally expressed in acute respiratory distress syndrome (ARDS) patients. However, its role and mechanism in pediatric ARDS process need further revealed.
Serum samples were selected from pediatric ARDS patients and age-matched healthy individuals. Lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs) were used to mimic ARDS cell models. Cell proliferation and apoptosis were tested by cell counting kit 8 assay, EdU assay, and flow cytometry. Oxidative stress and inflammation were assessed by corresponding kits. M1 macrophage polarization was evaluated via measuring CD86 positive cell rate. The expression levels of ICAM1, ubiquitin-specific peptidase 7 (USP7), and NF-κB pathway-related markers were detected by quantitative real-time PCR and western blot. The interaction between USP7 and ICAM1 was analyzed by Co-IP assay.
LPS induced apoptosis, inflammation, oxidative stress, and M1 macrophage polarization, while suppressed proliferation in HPMECs. ICAM1 was upregulated in pediatric ARDS patients, and its knockdown alleviated HPMEC injury induced by LPS. USP7 positively regulated ICAM1 protein expression through deubiquitination. USP7 overexpression aggravated LPS-induced HPMEC apoptosis, inflammation, oxidative stress, and M1 macrophage polarization. Besides, ICAM1 upregulation could eliminate the inhibitory effect of USP7 knockdown on LPS-induced HPMEC injury. In addition, USP7 activated NF-κB pathway by promoting ICAM1 expression.
USP7-mediated ICAM1 upregulation could promote LPS-induced HPMEC injury by activating NF-κB pathway, which provided a new idea for the treatment of pediatric ARDS.
细胞间黏附分子1（ICAM1）已被证实在急性呼吸窘迫综合征（ARDS）患者中异常表达。然而，其在小儿ARDS进程中的作用及机制尚需进一步揭示。
选取小儿ARDS患者及年龄匹配的健康个体的血清样本。采用脂多糖（LPS）诱导的人肺微血管内皮细胞（HPMECs）模拟ARDS细胞模型。通过细胞计数试剂盒8检测、EdU检测和流式细胞术检测细胞增殖和凋亡。通过相应试剂盒评估氧化应激和炎症。通过测量CD86阳性细胞率评估M1巨噬细胞极化。通过定量实时PCR和蛋白质免疫印迹法检测ICAM1、泛素特异性肽酶7（USP7）和NF-κB通路相关标志物的表达水平。通过免疫共沉淀法分析USP7与ICAM1之间的相互作用。
LPS诱导HPMECs凋亡、炎症、氧化应激和M1巨噬细胞极化，同时抑制其增殖。小儿ARDS患者中ICAM1上调，其敲低减轻了LPS诱导的HPMEC损伤。USP7通过去泛素化正向调节ICAM1蛋白表达。USP7过表达加重了LPS诱导的HPMEC凋亡、炎症、氧化应激和M1巨噬细胞极化。此外，ICAM1上调可消除USP7敲低对LPS诱导的HPMEC损伤的抑制作用。另外，USP7通过促进ICAM1表达激活NF-κB通路。
USP7介导的ICAM1上调可通过激活NF-κB通路促进LPS诱导的HPMEC损伤，这为小儿ARDS的治疗提供了新思路。
