KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction
Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promi...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/sci/5572221 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331475151847424 |
|---|---|
| author | Chen Wu Xin-Yue Zou Yi-Wen Jiang Da-Wei Lin Feng Jiang Yao-Sheng Wang |
| author_facet | Chen Wu Xin-Yue Zou Yi-Wen Jiang Da-Wei Lin Feng Jiang Yao-Sheng Wang |
| author_sort | Chen Wu |
| collection | DOAJ |
| description | Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K+ current (Kir), and decreased voltage-dependent K+ (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs. |
| format | Article |
| id | doaj-art-9f38f6571e3b48ebbe5cfae6e77bd6cb |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-9f38f6571e3b48ebbe5cfae6e77bd6cb2025-08-20T03:46:34ZengWileyStem Cells International1687-96782025-01-01202510.1155/sci/5572221KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial InfarctionChen Wu0Xin-Yue Zou1Yi-Wen Jiang2Da-Wei Lin3Feng Jiang4Yao-Sheng Wang5Department of CardiologyDepartment of CardiologyDepartment of CardiologyDepartment of CardiologyClinical Research and Innovation UnitDepartment of CardiologyCardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs. Kruppel-like factor 5 (KLF5) is a significant transcription factor involved in maintaining stem cell properties. In this study, we aimed to investigate whether overexpression of KLF5 could enhance the cardioprotective characteristics of BMSCs, particularly in terms of mitigating structural and electrical remodeling. Our in vivo experiments revealed that transplantation of KLF5-overexpressing BMSCs in mice with MI led to a substantial reduction in ventricular fibrosis and the occurrence of ventricular arrhythmias (VAs). In vitro coculture experiments demonstrated that BMSCs could inhibit CFs activation and cytoskeleton protein bundling induced by hypoxia through paracrine effects, resulting in reduced expression of α-SMA and Collagen I. Furthermore, coculturing BMSCs significantly reduced the expression of connexin 43, alleviated hypoxia, increased the expression of inward-rectifier K+ current (Kir), and decreased voltage-dependent K+ (Kv) currents. Mechanistically, KLF5 enhanced the effects of BMSCs by facilitating the transfer of miR-152-3 p from BMSCs-derived exosomes to CFs. Overall, our findings show that BMSCs transplantation promotes the recovery of cardiac function and reduces the incidence of arrhythmias by inhibiting CFs activation and modulating CFs Kir current remodeling. Additionally, overexpression of KLF5 enhances the cardioprotective effects of BMSCs.http://dx.doi.org/10.1155/sci/5572221 |
| spellingShingle | Chen Wu Xin-Yue Zou Yi-Wen Jiang Da-Wei Lin Feng Jiang Yao-Sheng Wang KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction Stem Cells International |
| title | KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction |
| title_full | KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction |
| title_fullStr | KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction |
| title_full_unstemmed | KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction |
| title_short | KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction |
| title_sort | klf5 regulation of exosome derived mir 152 3p from bone marrow stem cells improves ventricular arrhythmia after myocardial infarction |
| url | http://dx.doi.org/10.1155/sci/5572221 |
| work_keys_str_mv | AT chenwu klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction AT xinyuezou klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction AT yiwenjiang klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction AT daweilin klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction AT fengjiang klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction AT yaoshengwang klf5regulationofexosomederivedmir1523pfrombonemarrowstemcellsimprovesventriculararrhythmiaaftermyocardialinfarction |