The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts
Introduction: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular fun...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2015-12-01
|
| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320314539367 |
| _version_ | 1797285715451576320 |
|---|---|
| author | Tilde V Eskildsen Mikael Schneider Maria B Sandberg Vibe Skov Hasse Brønnum Mads Thomassen Torben A Kruse Ditte C Andersen Søren P Sheikh |
| author_facet | Tilde V Eskildsen Mikael Schneider Maria B Sandberg Vibe Skov Hasse Brønnum Mads Thomassen Torben A Kruse Ditte C Andersen Søren P Sheikh |
| author_sort | Tilde V Eskildsen |
| collection | DOAJ |
| description | Introduction: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular function including regulation of cardiac hypertrophy, heart failure and blood pressure possibly through AT 1 R signalling. However, the miR-132/212 targets in the heart remain unknown. Materials and methods: To understand the role of these miRNAs in cardiac signalling networks, we undertook comprehensive in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. Results: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors, signalling molecules and transcription factors. Subsequent comprehensive in silico analysis identified 24 target genes, of which 22 genes were qPCR validated. We identified seven genes involved in AngII signalling pathways. Conclusion: We here report novel insight of an extensive network of molecular pathways that fine-tuned by miR-132/212, suggesting a role for this miRNA family as master signalling switches in cardiac fibroblasts. Our data underscore the potential for miRNA tools to manipulate a large array of molecules and thereby control biological function. |
| first_indexed | 2024-03-07T18:07:15Z |
| format | Article |
| id | doaj.art-1efdfcb1f52d4ae1b9cb56aa2b2e8b1f |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T18:07:15Z |
| publishDate | 2015-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-1efdfcb1f52d4ae1b9cb56aa2b2e8b1f2024-03-02T08:32:49ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762015-12-011610.1177/1470320314539367The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblastsTilde V Eskildsen0Mikael Schneider1Maria B Sandberg2Vibe Skov3Hasse Brønnum4Mads Thomassen5Torben A Kruse6Ditte C Andersen7Søren P Sheikh8Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkDepartment of Clinical Genetics, Odense University Hospital, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkDepartment of Clinical Genetics, Odense University Hospital, DenmarkDepartment of Clinical Genetics, Odense University Hospital, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, DenmarkIntroduction: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular function including regulation of cardiac hypertrophy, heart failure and blood pressure possibly through AT 1 R signalling. However, the miR-132/212 targets in the heart remain unknown. Materials and methods: To understand the role of these miRNAs in cardiac signalling networks, we undertook comprehensive in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. Results: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors, signalling molecules and transcription factors. Subsequent comprehensive in silico analysis identified 24 target genes, of which 22 genes were qPCR validated. We identified seven genes involved in AngII signalling pathways. Conclusion: We here report novel insight of an extensive network of molecular pathways that fine-tuned by miR-132/212, suggesting a role for this miRNA family as master signalling switches in cardiac fibroblasts. Our data underscore the potential for miRNA tools to manipulate a large array of molecules and thereby control biological function.https://doi.org/10.1177/1470320314539367 |
| spellingShingle | Tilde V Eskildsen Mikael Schneider Maria B Sandberg Vibe Skov Hasse Brønnum Mads Thomassen Torben A Kruse Ditte C Andersen Søren P Sheikh The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts Journal of the Renin-Angiotensin-Aldosterone System |
| title | The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts |
| title_full | The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts |
| title_fullStr | The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts |
| title_full_unstemmed | The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts |
| title_short | The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts |
| title_sort | microrna 132 212 family fine tunes multiple targets in angiotensin ii signalling in cardiac fibroblasts |
| url | https://doi.org/10.1177/1470320314539367 |
| work_keys_str_mv | AT tildeveskildsen themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT mikaelschneider themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT mariabsandberg themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT vibeskov themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT hassebrønnum themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT madsthomassen themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT torbenakruse themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT dittecandersen themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT sørenpsheikh themicrorna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT tildeveskildsen microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT mikaelschneider microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT mariabsandberg microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT vibeskov microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT hassebrønnum microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT madsthomassen microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT torbenakruse microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT dittecandersen microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts AT sørenpsheikh microrna132212familyfinetunesmultipletargetsinangiotensiniisignallingincardiacfibroblasts |