Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

Kim, Jihoon; Shimizu, Chisato; He, Ming; Wang, Hao; Hoffman, Hal M.; Tremoulet, Adriana H.; Shyy, John Y.-J.; Burns, Jane C.

doi:10.3390/ijms241512318

Open AccessArticle

Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

by

Jihoon Kim

^1,2,†,

Chisato Shimizu

^3,*,†,

Ming He

⁴,

Hao Wang

³

,

Hal M. Hoffman

^3,5,

Adriana H. Tremoulet

^3,5,

John Y.-J. Shyy

⁴ and

Jane C. Burns

^3,5

¹

Department of Biomedical Informatics, University of California, San Diego, CA 92093, USA

²

Section of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT 06510, USA

³

Department of Pediatrics, University of California, San Diego, CA 92093, USA

⁴

Department of Medicine, University of California, San Diego, CA 92093, USA

⁵

Rady Children’s Hospital, San Diego, CA 92123, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(15), 12318; https://doi.org/10.3390/ijms241512318

Submission received: 3 July 2023 / Revised: 26 July 2023 / Accepted: 28 July 2023 / Published: 1 August 2023

(This article belongs to the Special Issue Contribution of Endothelial Dysfunction to Neurovascular and Cardiovascular Diseases)

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Abstract

Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n = 5), MIS-C (n = 7), and healthy controls (n = 3). We conducted a weighted gene co-expression network analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using relaxed filtering (unadjusted p < 0.05, >1.1-fold difference). We found seven gene modules in MIS-C, annotated as an increased TNFα/NFκB pathway, decreased EC homeostasis, anti-inflammation and immune response, translation, and glucocorticoid responsive genes and endothelial–mesenchymal transition (EndoMT). To further understand the difference in the EC response between MIS-C and KD, stringent filtering was applied to identify 41 differentially expressed genes (DEGs) between MIS-C and KD (adjusted p < 0.05, >2-fold-difference). Again, in MIS-C, NFκB pathway genes, including nine pro-survival genes, were upregulated. The expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts but reduced transcripts related to EndoMT and EC homeostasis. These differences in the EC response may influence the different cardiovascular outcomes in these two diseases.

Keywords: Kawasaki disease; MIS-C; endothelial cell; WGCNA; network analysis; NFκB pathway; apoptosis; autophagy; EndoMT; RNA-seq

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MDPI and ACS Style

Kim, J.; Shimizu, C.; He, M.; Wang, H.; Hoffman, H.M.; Tremoulet, A.H.; Shyy, J.Y.-J.; Burns, J.C. Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. Int. J. Mol. Sci. 2023, 24, 12318. https://doi.org/10.3390/ijms241512318

AMA Style

Kim J, Shimizu C, He M, Wang H, Hoffman HM, Tremoulet AH, Shyy JY-J, Burns JC. Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. International Journal of Molecular Sciences. 2023; 24(15):12318. https://doi.org/10.3390/ijms241512318

Chicago/Turabian Style

Kim, Jihoon, Chisato Shimizu, Ming He, Hao Wang, Hal M. Hoffman, Adriana H. Tremoulet, John Y.-J. Shyy, and Jane C. Burns. 2023. "Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children" International Journal of Molecular Sciences 24, no. 15: 12318. https://doi.org/10.3390/ijms241512318

APA Style

Kim, J., Shimizu, C., He, M., Wang, H., Hoffman, H. M., Tremoulet, A. H., Shyy, J. Y.-J., & Burns, J. C. (2023). Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. International Journal of Molecular Sciences, 24(15), 12318. https://doi.org/10.3390/ijms241512318

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Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

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