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MiR-223-3p Alleviates Vascular Endothelial Injury by Targeting IL6ST in Kawasaki Disease
- Source :
- Frontiers in Pediatrics, Frontiers in Pediatrics, Vol 7 (2019)
- Publication Year :
- 2019
- Publisher :
- Frontiers Media SA, 2019.
-
Abstract
- Background: Kawasaki disease (KD) is a self-limiting illness with acute systematic vascular inflammation. It causes pathological changes in mostly medium and small-sized arteries, especially the arteria coronaria, which adds the risk of developing coronary heart disease in adults. Materials and methods: We detected the miR-223-3p expression in 30 KD patients combined with 12 normal controls using miRNA microarrays and RT-PCR. A KD mouse model was constructed using Candida albicans water insoluble substance (CAWS). We also checked the miR-223-3p's expression using qRT-PCR. The Luciferase reporting system was implemented to validate the correlation between miR-223-3p and Interleukin-6 receptor subunit beta (IL-6ST). TNF-α was used to stimulate human coronary artery endothelial cells (HCAECs), and miR-223-3p activator or inhibitor and KD serum were used to treat HCAECs. A Western blotting automatic quantitative analysis protein imprinting system was used to test the expression of signal transducer and the activator of transcription 3 (STAT3), phosphorylated-signal transducer and the activator of transcription 3 (pSTAT3) and NF-κB p65. Results: Clinical trials found that miR-223-3p expressions were markedly different (more than 2-fold) between the acute KD group and the control group. E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) levels were also significantly higher (about 2-fold) in KD especially with coronary artery lesions. MiR-223-3p could alleviate vascular endothelial damage in KD mice, and IL-6 (Interleukin-6), E-selectin and ICAM-1 were simultaneously negative. The values of IL-6, E-selectin, and ICAM-1 mRNA expressions decreased, while the value of IL-6ST was increased between the agonist treated mice and KD mice. The RT-qPCR consequences displayed that miR-223-3p explored the highest expression on the third day in both the KD mice as well as the agonist group. MiR-223-3p can directly combine with IL-6ST 3' untranslatable regions (UTR) and held back the IL-6's expression. Overexpression of miR-223 down regulated IL6ST expression and decreased the expression of p-STAT3 and NF-κB p65, while the miR-223 inhibitor could reverse the above process. Conclusion: MiR-223-3p is an important regulatory factor of vascular endothelial damage in KD and could possibly become a potential target of KD treatment in the future.
- Subjects :
- Agonist
medicine.medical_specialty
medicine.drug_class
030204 cardiovascular system & hematology
Pediatrics
STAT3
03 medical and health sciences
0302 clinical medicine
mir-223
030225 pediatrics
Internal medicine
microRNA
medicine
vascular endothelial damage
Original Research
Messenger RNA
Kawasaki disease
biology
business.industry
Activator (genetics)
lcsh:RJ1-570
lcsh:Pediatrics
medicine.disease
Blot
Endocrinology
Pediatrics, Perinatology and Child Health
biology.protein
business
MicroRNA-223-3p
IL6ST
Subjects
Details
- ISSN :
- 22962360
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pediatrics
- Accession number :
- edsair.doi.dedup.....9fbd3708d550833ad09fa9508330e8de