Jinsong Tao1,2, Jingyi Wang3, Chunyu Li4, Weiwei Wang4, Hao Yu5, Jinhui Liu6, Xiangqing Kong1, Yan Chen5,7. 1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 2. Department of Cardiology, The Affiliated Hospital of Southeast University Medical College, Jiangyin 214400, China. 3. Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 4. Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 5. Emergency Center, Kizilsu Kirghiz Autonomous Prefecture People's Hospital, Artux 845350, China. 6. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 7. Emergency Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Abstract
BACKGROUND: Heart failure (HF) is a progressive disease with relatively poor prognosis and lacks effective therapy, and the discovery of dysregulated microRNAs (miRNAs) and their role in cardiac fibroblasts have provided a new avenue for elucidating the mechanism involved in HF. METHODS: Two datasets of GSE53080 and GSE57338 were used to screen the miRNAs profiling and analysis the differentially expressed genes (DEGs) in HF. QRT-PCR was used to detect miR-216a between HF and healthy controls (HC). Cell counting kit-8 (CCK-8) assay and clonogenic assay were used to analyze the effect of proliferation and fibrogenesis. Then dual-luciferase activity assay and western blotting were used to confirm the key mechanism. RESULTS: In this study, the results showed that miR-216a was significantly up-regulated in HF and over-expression of miR-216a promoted proliferation and enhanced the fibrogenesis in the human cardiac fibroblasts (HCF) cells. Phosphatase and tensin homolog (PTEN) and mothers against decapentaplegic homolog 7 (SMAD7) were both validated as the direct target genes of miR-216a, which were confirmed by the dual-luciferase reporter assay. MiR-216a decreased the expression of PTEN and SMAD7 leading to the activation of Akt/mTOR and TGF-βRI/Smad2 in the HCF cells, which might act as a promoter of cardiac fibrosis. CONCLUSIONS: Our study might provide a promising approach for the treatment of HF in the future. 2019 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: Heart failure (HF) is a progressive disease with relatively poor prognosis and lacks effective therapy, and the discovery of dysregulated microRNAs (miRNAs) and their role in cardiac fibroblasts have provided a new avenue for elucidating the mechanism involved in HF. METHODS: Two datasets of GSE53080 and GSE57338 were used to screen the miRNAs profiling and analysis the differentially expressed genes (DEGs) in HF. QRT-PCR was used to detect miR-216a between HF and healthy controls (HC). Cell counting kit-8 (CCK-8) assay and clonogenic assay were used to analyze the effect of proliferation and fibrogenesis. Then dual-luciferase activity assay and western blotting were used to confirm the key mechanism. RESULTS: In this study, the results showed that miR-216a was significantly up-regulated in HF and over-expression of miR-216a promoted proliferation and enhanced the fibrogenesis in the human cardiac fibroblasts (HCF) cells. Phosphatase and tensin homolog (PTEN) and mothers against decapentaplegic homolog 7 (SMAD7) were both validated as the direct target genes of miR-216a, which were confirmed by the dual-luciferase reporter assay. MiR-216a decreased the expression of PTEN and SMAD7 leading to the activation of Akt/mTOR and TGF-βRI/Smad2 in the HCF cells, which might act as a promoter of cardiac fibrosis. CONCLUSIONS: Our study might provide a promising approach for the treatment of HF in the future. 2019 Cardiovascular Diagnosis and Therapy. All rights reserved.
Entities:
Keywords:
Heart failure (HF); cardiac fibroblasts; miR-216a; mothers against decapentaplegic homolog 7 (SMAD7); phosphatase and tensin homolog (PTEN)
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