USP7-Mediated ICAM1 Facilitates Lipopolysaccharide-Induced Human Pulmonary Microvascular Endothelial Cell Injury to Accelerate Pediatric Acute Respiratory Distress Syndrome.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.