Cardiovascular therapeutics · 2022
MicroRNA-325-3p Targets Human Epididymis Protein 4 to Relieve Right Ventricular Fibrosis in Rats with Pulmonary Arterial Hypertension.
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Tang Yi, Huo Xiaowei, Liu Junyu, Tang Yijin, Zhang Min, Xie Wenlin, Zheng Zhaofen, He Jin, Lian Jiayan
Аннотация
BACKGROUND: Pulmonary arterial hypertension (PAH) usually causes right ventricular dysfunction, which is closely related to cardiac fibrosis. But cardiac fibrosis mechanism remains unclear. Our purpose was to explore microRNA-325-3p (miR-325-3p)/human epididymis protein 4's (HE4) role in the occurrence and development of right ventricular fibrosis in PAH.
METHODS: The right ventricular fibrosis model of rats with PAH was constructed, and miR-325-3p was overexpressed to explore miR-325-3p's effect on myocardial fibrosis in rats with PAH. Pearson correlation coefficient examined the correlation between HE4 and miR-325-3p. We separated and identified the primary rat myocardial fibroblasts from the heart tissue. Then, the Ang II-treated myocardial fibroblast fibrosis model was constructed. miR-325-3p mimics and si-HE4 and oe-HE4 cell lines were constructed to investigate miR-325-3p and HE4 effects on myocardial cell fibrosis. Then, we added PI3K inhibitor LY294002 to study the effects of HE4 in cell fibrosis by the PI3K/AKT pathway. Starbase was used to predict miR-325-3p and HE4 binding sites. Dual-luciferase reporter assay verified whether miR-325-3p and HE4 were targeted.
RESULTS: Overexpression of miR-325-3p alleviated myocardial fibrosis in rats with PAH. Pearson correlation coefficient showed that HE4 was negatively correlated with miR-325-3p expression. Starbase predicted that miR-325-3p had binding sites with HE4. Dual-luciferase reporter assay demonstrated that miR-325-3p targeted HE4. Overexpression of miR-325-3p downregulated HE4 and inhibited myocardial fibroblast fibrosis. HE4 knockdown inhibited myocardial fibroblast fibrosis. HE4 promoted myocardial fibroblast fibrosis and activated the PI3K/AKT pathway. In addition, HE4 affected myocardial fibroblast fibrosis through the PI3K/AKT pathway.
CONCLUSIONS: miR-325-3p could target HE4 to relieve right ventricular fibrosis in rats with PAH. This study could provide new targets and strategies for right ventricular fibrosis in PAH.
METHODS: The right ventricular fibrosis model of rats with PAH was constructed, and miR-325-3p was overexpressed to explore miR-325-3p's effect on myocardial fibrosis in rats with PAH. Pearson correlation coefficient examined the correlation between HE4 and miR-325-3p. We separated and identified the primary rat myocardial fibroblasts from the heart tissue. Then, the Ang II-treated myocardial fibroblast fibrosis model was constructed. miR-325-3p mimics and si-HE4 and oe-HE4 cell lines were constructed to investigate miR-325-3p and HE4 effects on myocardial cell fibrosis. Then, we added PI3K inhibitor LY294002 to study the effects of HE4 in cell fibrosis by the PI3K/AKT pathway. Starbase was used to predict miR-325-3p and HE4 binding sites. Dual-luciferase reporter assay verified whether miR-325-3p and HE4 were targeted.
RESULTS: Overexpression of miR-325-3p alleviated myocardial fibrosis in rats with PAH. Pearson correlation coefficient showed that HE4 was negatively correlated with miR-325-3p expression. Starbase predicted that miR-325-3p had binding sites with HE4. Dual-luciferase reporter assay demonstrated that miR-325-3p targeted HE4. Overexpression of miR-325-3p downregulated HE4 and inhibited myocardial fibroblast fibrosis. HE4 knockdown inhibited myocardial fibroblast fibrosis. HE4 promoted myocardial fibroblast fibrosis and activated the PI3K/AKT pathway. In addition, HE4 affected myocardial fibroblast fibrosis through the PI3K/AKT pathway.
CONCLUSIONS: miR-325-3p could target HE4 to relieve right ventricular fibrosis in rats with PAH. This study could provide new targets and strategies for right ventricular fibrosis in PAH.