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Mechanism exploration of miRNA-205-3p in Kawasaki disease combined with giant coronary artery aneurysm#br# |
ZHENG Yang ZHANG Hui LI Xiaohui ZHANG Mingming LIN Yao SHI Lin#br# |
Department of Cardiovascular, Children’s Hospital Capital Institute of Pediatrics, Beijing 100020, China
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Abstract Objective To explore the role and potential mechanism of human miRNA-205-3p in children with Kawasaki disease (KD) and KD combined with giant coronary artery aneurysm (GCAA). Methods Thirty-six children with KD were hospitalized in Department of Cardiology, Children’s Hospital Capital Institute of Pediatrics from November 2018 to February 2021, included 30 cases in KD group, and six cases in KD combined with GCAA group. There were 20 healthy children and 20 febrile children matched by age and sex in the same period (KD group and KD combined with GCAA group: healthy control group: fever control group = 1.8∶1∶1). The differentially expressed miRNA in KD group, KD combined with GCAA group, healthy control group, and fever control group were screened by microarray. Fluorescence quantitative polymerase chain reaction (qPCR) was used for verification. Possible related regulatory pathways were explored by bioinformatics analysis. Twelve C57BL/6 SPF male mice aged three to four weeks were divided into KD combined with coronary artery injury (CAL) group and control group according to random number table method, with six mice in each group. The animal model of KD combined with CAL was established by intraperitoneal injection of Lactobacillus casei cell wall components. Transforming growth factor-β1 (TGF-β1) and SMAD5 mRNA expressions in mice heart tissue were analyzed by fluorescence qPCR. Results Twelve miRNAs with more than 10 fold differential expression were screened by microarray. The expression of miRNA-205-3p in KD group was significantly higher than that in healthy control group and fever control group, and the difference was statistically significant (P < 0.05). The expression of miRNA-205-3p in KD combined with GCAA group was significantly higher than that in healthy control group, fever control group, and KD group, and the differences were statistically significant (P < 0.05). Bioinformatic analysis suggested miRNA-205-3p might regulate KD and GCAA formation through TGF-β/SMAD5 signaling pathway. TGF-β1 and SMAD5 mRNA expressions in mice heart tissue of KD combined with CAL group were higher than those in control group, the differences were statistically significant (P < 0.05). Conclusion miRNA-205-3p can play a role in the formation of KD and KD combined with GCAA through TGF-β/SMAD5 signaling pathway. This research identifies a new target for clinical intervention in the formation of KD combined with GCAA.
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