Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p
Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Rapid electrical stimulation (RES) of atrial fibroblasts plays a crucial role in AF pathogenesis, but the underlying molecular mechanisms remain unclear. This study investigates t...
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2024-11-01
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| author | Cheng-Yen Chuang Bao-Wei Wang Ying-Ju Yu Wei-Jen Fang Chiu-Mei Lin Kou-Gi Shyu Su-Kiat Chua |
| author_facet | Cheng-Yen Chuang Bao-Wei Wang Ying-Ju Yu Wei-Jen Fang Chiu-Mei Lin Kou-Gi Shyu Su-Kiat Chua |
| author_sort | Cheng-Yen Chuang |
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| description | Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Rapid electrical stimulation (RES) of atrial fibroblasts plays a crucial role in AF pathogenesis, but the underlying molecular mechanisms remain unclear. This study investigates the regulatory axis involving MALAT1, miR-499a-5p, and SOX6 in human cardiac fibroblasts from adult atria (HCF-aa) under RES conditions. Methods: HCF-aa were subjected to RES at 0.5 V/cm and 10 Hz. The expression levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-499a-5p, and SRY-Box Transcription Factor 6 (SOX6) were measured using qPCR and Western blot analyses. Luciferase reporter assays were performed to confirm target relationships. The effects of MALAT1 siRNA, miR-499a-5p mimics/inhibitors, and SOX6 overexpression on gene expression and apoptosis were assessed. Results: RES increased exosomal MALAT1 expression, peaking at 2 h. MiR-499a-5p levels initially increased, then decreased at 2 h, coinciding with peak MALAT1 expression. SOX6 mRNA and protein levels increased, peaking at 4 and 6 h, respectively. Luciferase assays confirmed MALAT1 and SOX6 as miR-499a-5p targets. MALAT1 knockdown increased miR-499a-5p levels and reduced SOX6 expression. MiR-499a-5p overexpression decreased SOX6 levels and inhibited RES-induced apoptosis. Conclusion: In HCF-aa under RES, increased exosomal MALAT1 expression counteracts miR-499-5p’s suppression of SOX6, suggesting that MALAT1-containing exsosomes derived from HCF-aa may offer a novel cell-free therapeutic approach for AF. |
| format | Article |
| id | doaj-art-22f640d725af42108f24fa39a7c1c848 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-22f640d725af42108f24fa39a7c1c8482024-12-13T16:24:04ZengMDPI AGCells2073-44092024-11-011323194210.3390/cells13231942Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5pCheng-Yen Chuang0Bao-Wei Wang1Ying-Ju Yu2Wei-Jen Fang3Chiu-Mei Lin4Kou-Gi Shyu5Su-Kiat Chua6Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDivision of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanBackground: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant morbidity and mortality. Rapid electrical stimulation (RES) of atrial fibroblasts plays a crucial role in AF pathogenesis, but the underlying molecular mechanisms remain unclear. This study investigates the regulatory axis involving MALAT1, miR-499a-5p, and SOX6 in human cardiac fibroblasts from adult atria (HCF-aa) under RES conditions. Methods: HCF-aa were subjected to RES at 0.5 V/cm and 10 Hz. The expression levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-499a-5p, and SRY-Box Transcription Factor 6 (SOX6) were measured using qPCR and Western blot analyses. Luciferase reporter assays were performed to confirm target relationships. The effects of MALAT1 siRNA, miR-499a-5p mimics/inhibitors, and SOX6 overexpression on gene expression and apoptosis were assessed. Results: RES increased exosomal MALAT1 expression, peaking at 2 h. MiR-499a-5p levels initially increased, then decreased at 2 h, coinciding with peak MALAT1 expression. SOX6 mRNA and protein levels increased, peaking at 4 and 6 h, respectively. Luciferase assays confirmed MALAT1 and SOX6 as miR-499a-5p targets. MALAT1 knockdown increased miR-499a-5p levels and reduced SOX6 expression. MiR-499a-5p overexpression decreased SOX6 levels and inhibited RES-induced apoptosis. Conclusion: In HCF-aa under RES, increased exosomal MALAT1 expression counteracts miR-499-5p’s suppression of SOX6, suggesting that MALAT1-containing exsosomes derived from HCF-aa may offer a novel cell-free therapeutic approach for AF.https://www.mdpi.com/2073-4409/13/23/1942microRNA-499a-5pMALAT1sox-6rapid electrical stimulationapoptosis |
| spellingShingle | Cheng-Yen Chuang Bao-Wei Wang Ying-Ju Yu Wei-Jen Fang Chiu-Mei Lin Kou-Gi Shyu Su-Kiat Chua Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p Cells microRNA-499a-5p MALAT1 sox-6 rapid electrical stimulation apoptosis |
| title | Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p |
| title_full | Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p |
| title_fullStr | Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p |
| title_full_unstemmed | Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p |
| title_short | Exosomal MALAT1 from Rapid Electrical Stimulation-Treated Atrial Fibroblasts Enhances Sox-6 Expression by Downregulating miR-499a-5p |
| title_sort | exosomal malat1 from rapid electrical stimulation treated atrial fibroblasts enhances sox 6 expression by downregulating mir 499a 5p |
| topic | microRNA-499a-5p MALAT1 sox-6 rapid electrical stimulation apoptosis |
| url | https://www.mdpi.com/2073-4409/13/23/1942 |
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