Preliminary exploration of the role of CD14 mRNA in coronary artery injury in Kawasaki disease

Kun Zhu; Bo Wang; Huijuan Kan; Xiaoling Li; Xi Wang; Kangping Xu; Yu Pu; Zaidong Liu; Dongkai Wei; Wenhua Yan

doi:10.62347/GFSG6634

Preliminary exploration of the role of CD14 mRNA in coronary artery injury in Kawasaki disease

Am J Transl Res. 2024 Nov 15;16(11):6867-6888. doi: 10.62347/GFSG6634. eCollection 2024.

Authors

Kun Zhu^{1

2}, Bo Wang¹, Huijuan Kan³, Xiaoling Li⁴, Xi Wang⁴, Kangping Xu⁴, Yu Pu⁴, Zaidong Liu⁴, Dongkai Wei⁴, Wenhua Yan¹

Affiliations

¹ Department of Cardiology, Children's Hospital of Soochow University Suzhou, Jiangsu, China.
² Department of Paediatrics, The First People's Hospital of Yan Cheng Yancheng, Jiangsu, China.
³ Department of Paediatrics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu, China.
⁴ Suzhou Func Biotech Inc. Suzhou, Jiangsu, China.

Abstract

Objective: Kawasaki disease (KD) is an acute vasculitis that typically occurs in young children and may lead to coronary artery lesions (CALs), but the precise mechanisms that trigger this illness are unclear. We hope to identify some clues to the pathogenesis of KD through clinical sample analysis.

Methods: We included 12 children who had been diagnosed with KD coronary artery lesions (KD-CALs) or KD-no coronary artery lesions (KD-nCALs) and investigated the transcriptome variations of patients with KD in the acute and subacute stages. Further, we enrolled 12 new patients with KD and investigated the expression of CD14 mRNA and the downstream genes A20, A1/BF1_1, and IκBα, via real-time quantitative PCR (qRT-PCR). In addition, we established an animal model of KD-induced coronary inflammation and measured the protein levels of mCD14, IκBα and IL-6 on Day 7 and 14 after completion of modelling. Then, molecular docking was applied to analyse the binding power of the chemical compounds with mCD14.

Results: The KD-CALs group contained 62 differentially expressed genes (DEGs), which were enriched in the nuclear factor kappa-B (NF-κB) signalling pathway. CD14 mRNA was upregulated in the acute stage, which caused an increase in expression of the downstream genes A20, A1/BF1_1, and IκBα. Molecular docking revealed that the best docking medicine with mCD14 was lupenone. On Day 14 after modelling, there was significant inflammation with infiltration of lymphocytes and macrophages in the coronary endothelium of the mice. Compared with those in the Day 7 group and the control group, the levels of mCD14, IκBα and IL-6 proteins in the coronary endothelium significantly increased in mice in the Day 14 group.

Conclusions: CD14 mRNA may regulate IκBα expression and subsequently activate the NF-κB signalling pathway, ultimately causing vasculitis. CD14 mRNA participates in the occurrence of coronary artery injury, and its protein product mCD14 may be a potential therapeutic target for KD-CALs.

Keywords: CD14 mRNA; Kawasaki disease; RNA-seq; coronary artery lesions.