Semaphorin 7A promotes endothelial permeability and inflammation via plexin C1 and integrin β1 in Kawasaki disease.
Humans
Semaphorins
/ metabolism
Mucocutaneous Lymph Node Syndrome
/ metabolism
Male
Female
Antigens, CD
/ metabolism
Integrin beta1
/ metabolism
Child, Preschool
Receptors, Cell Surface
/ metabolism
Case-Control Studies
Inflammation
/ metabolism
Infant
Nerve Tissue Proteins
/ metabolism
Endothelial Cells
/ metabolism
Child
Cells, Cultured
ADAM17 Protein
/ metabolism
Endothelium, Vascular
/ metabolism
Monocytes
/ metabolism
Capillary Permeability
GPI-Linked Proteins
Endothelial cell
Inflammation
Kawasaki disease
Semaphorin 7A
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
27 Apr 2024
27 Apr 2024
Historique:
received:
11
09
2023
accepted:
16
04
2024
medline:
28
4
2024
pubmed:
28
4
2024
entrez:
27
4
2024
Statut:
epublish
Résumé
Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1β, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin β1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin β1-dependent manner, while both plexin C1 and integrin β1 contributed to Sema7A-induced HCAEC hyperpermeability. Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin β1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
Sections du résumé
BACKGROUND
BACKGROUND
Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions.
METHODS
METHODS
Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1β, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran.
RESULTS
RESULTS
The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin β1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin β1-dependent manner, while both plexin C1 and integrin β1 contributed to Sema7A-induced HCAEC hyperpermeability.
CONCLUSIONS
CONCLUSIONS
Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin β1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
Identifiants
pubmed: 38678170
doi: 10.1186/s12887-024-04766-3
pii: 10.1186/s12887-024-04766-3
doi:
Substances chimiques
Semaphorins
0
SEMA7A protein, human
0
Antigens, CD
0
Integrin beta1
0
Receptors, Cell Surface
0
Nerve Tissue Proteins
0
ADAM17 Protein
EC 3.4.24.86
ADAM17 protein, human
EC 3.4.24.86
GPI-Linked Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
285Subventions
Organisme : Natural Science Foundation of Shaanxi Province
ID : 2023-JC-YB-718
Organisme : Natural Science Foundation of Shaanxi Province
ID : 2024JC-YBQN-0869
Organisme : Science and Technology Plan Project of Weiyang District Xi'an City
ID : 202222
Organisme : Scientific Research Capacity Improvement Project of Xi'an Medical University
ID : 2022NLTS107
Organisme : Scientific Research Project of Xi'an Health Commission
ID : 2023qn12
Informations de copyright
© 2024. The Author(s).
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