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Combined high-throughput library screening and next generation RNA sequencing uncover microRNAs controlling human cardiac fibroblast biology.
Schimmel, Katharina; Stojanovic, Stevan D; Huang, Cheng-Kai; Jung, Mira; Meyer, Martin H; Xiao, Ke; Grote-Levi, Lea; Bär, Christian; Pfanne, Angelika; Mitzka, Saskia; Just, Annette; Geffers, Robert; Bock, Katharina; Kenneweg, Franziska; Kleemiß, Felix; Falk, Christine S; Fiedler, Jan; Thum, Thomas.
Afiliación
  • Schimmel K; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Stojanovic SD; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Huang CK; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Jung M; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Meyer MH; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Xiao K; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Grote-Levi L; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Bär C; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Pfanne A; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Mitzka S; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Just A; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Geffers R; Helmholtz Centre for Infection Research, Research Group Genome Analytics, Braunschweig, Germany.
  • Bock K; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Kenneweg F; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Kleemiß F; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Falk CS; Transplant Immunology, Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Germany.
  • Fiedler J; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.
  • Thum T; Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany; REBIRTH Excellence Cluster, Hannover Medical School, Hannover, Germany. Electronic address: Thum.Thomas@mh-hannover.de.
J Mol Cell Cardiol ; 150: 91-100, 2021 01.
Article en En | MEDLINE | ID: mdl-33127387
BACKGROUND: Myocardial fibrosis is a hallmark of the failing heart, contributing to the most common causes of deaths worldwide. Several microRNAs (miRNAs, miRs) controlling cardiac fibrosis were identified in recent years; however, a more global approach to identify miRNAs involved in fibrosis is missing. METHODS AND RESULTS: Functional miRNA mimic library screens were applied in human cardiac fibroblasts (HCFs) to identify annotated miRNAs inducing proliferation. In parallel, miRNA deep sequencing was performed after subjecting HCFs to proliferating and resting stimuli, additionally enabling discovery of novel miRNAs. In-depth in vitro analysis confirmed the pro-fibrotic nature of selected, highly conserved miRNAs miR-20a-5p and miR-132-3p. To determine downstream cellular pathways and their role in the fibrotic response, targets of the annotated miRNA candidates were modulated by synthetic siRNA. We here provide evidence that repression of autophagy and detoxification of reactive oxygen species by miR-20a-5p and miR-132-3p explain some of their pro-fibrotic nature on a mechanistic level. CONCLUSION: We here identified both miR-20a-5p and miR-132-3p as crucial regulators of fibrotic pathways in an in vitro model of human cardiac fibroblast biology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biblioteca de Genes / Análisis de Secuencia de ARN / MicroARNs / Secuenciación de Nucleótidos de Alto Rendimiento / Fibroblastos / Miocardio Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans Idioma: En Revista: J Mol Cell Cardiol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biblioteca de Genes / Análisis de Secuencia de ARN / MicroARNs / Secuenciación de Nucleótidos de Alto Rendimiento / Fibroblastos / Miocardio Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans Idioma: En Revista: J Mol Cell Cardiol Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido