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Matthias S Leisegang1, Christian Fork1, Ivana Josipovic1

  • 1From Institute for Cardiovascular Physiology (M.S.L., C.F., I.J., M.J.M., J.E., F.M., R.P.B.), Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine (F.M.R., J.H., I.W.), Institute of Vascular Signalling (J.H.), Institute of Cardiovascular Regeneration (P.H. Y.P., S.U., K.S., R.A.B., S.D.), Department of Neurosurgery (T.M.F.), Pharmazentrum Frankfurt, Institute of General Pharmacology and Toxicology (K.D.), Goethe University, Germany; ECCPS Bioinformatics and Sequencing Facility (J.P., S.G., C.K., M.L.) and Department of Lung Development and Remodeling (C.V., S.S.P.), Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany; Institute of Neurology (K.H.P., M.M., K.D.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany (L.M.); Luxembourg Centre of Neuropathology (M.M.); Laboratoire National de Santé, Dudelange, Luxembourg (M.M.); Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette (M.M.); NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (M.M.); Cardiovascular Innovation Institute, University of Louisville, KY (S.U.); Department of Internal Medicine, Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany (R.T.S., N.W., S.S.P.); Department of Medicine, Duke University and Durham VA Medical Center, NC (F.J.M.); and German Center of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt, Germany (M.S.L., C.F., I.J., J.H., J.E., P.H., F.M., Y.P., K.H.P., K.S., I.W., R.A.B., S.D., R.P.B.).

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PubMed
Resumen
Este resumen es generado por máquina.

Este estudio identifica a MANTIS, un nuevo ARN largo no codificante (ARNlnc), como crucial para la función de las células endoteliales y la angiogénesis. MANTIS regula la transcripción génica mediante la interacción con los complejos de remodelación de la cromatina.

Palabras clave:
ARN largo no codificanteLa epigenomíael glioblastomahipertensión pulmonarNeovascularización fisiológica

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Área de la Ciencia:

  • Biología molecular
  • La genética
  • Biología celular

Sus antecedentes:

  • La función angiogénica de las células endoteliales es vital, pero se entiende incompletamente.
  • El papel de los ARN largos no codificantes (ARNlnc) en la regulación de las células endoteliales es en gran medida inexplorado.

Objetivo del estudio:

  • Identificar nuevos lncRNAs endoteliales funcionalmente significativos
  • Investigar los mecanismos reguladores y el impacto funcional de los lncRNA identificados.

Principales métodos:

  • Análisis de matriz de exones y eliminación de JARID1B en las células endotelial de la vena umbilical humana.
  • Descarga de ARN, espectrometría de masas, seguimiento de ChIP, CRISPR-Cas9 y análisis de la expresión génica.
  • Análisis de muestras de pacientes (pulmón, glioblastoma) y modelos animales (aterosclerosis, hipertensión pulmonar).

Principales resultados:

  • Se identificó a MANTIS (lncRNA n342419) como un lncRNA epigenéticamente regulado clave.
  • La expresión de MANTIS está alterada en la hipertensión pulmonar, la aterosclerosis y el glioblastoma.
  • La deleción/ silenciamiento de MANTIS altera la angiogénesis de las células endoteliales y la respuesta al estrés de cizallamiento.
  • MANTIS interactúa con BRG1 para regular la remodelación de la cromatina y la transcripción de genes endoteliales clave (SOX18, SMAD6, COUP-TFII).

Conclusiones:

  • MANTIS es un nuevo lncRNA regulado diferencialmente.
  • MANTIS juega un papel crítico en la facilitación de la función angiogénica endotelial.
  • MANTIS representa un objetivo terapéutico potencial para las enfermedades vasculares.