High-content analysis of microRNAs involved in the phenotype regulation of vascular smooth muscle cells

• Verfasst von: Zhang, Jian [VerfasserIn]
• Verfasst von: Starkuviene-Erfle, Vytaute [VerfasserIn]
• Verfasst von: Erfle, Holger [VerfasserIn]
• Verfasst von: Wang, Zhaohui [VerfasserIn]
• Verfasst von: Gunkel, Manuel [VerfasserIn]
• Verfasst von: Zeng, Ziwei [VerfasserIn]
• Verfasst von: Sticht, Carsten [VerfasserIn]
• Verfasst von: Kan, Kejia [VerfasserIn]
• Verfasst von: Rahbari, Nuh Nabi [VerfasserIn]
• Verfasst von: Keese, Michael [VerfasserIn]
• Titel: High-content analysis of microRNAs involved in the phenotype regulation of vascular smooth muscle cells
• Verf.angabe: Jian Zhang, Vytaute Starkuviene, Holger Erfle, Zhaohui Wang, Manuel Gunkel, Ziwei Zeng, Carsten Sticht, Kejia Kan, Nuh Rahbari & Michael Keese
• E-Jahr: 2022
• Jahr: 03 März 2022
• Umfang: 14 S.
• Fussnoten: Gesehen am 18.04.2023
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Springer Nature, 2011
• Jahr Quelle: 2022
• Band/Heft Quelle: 12(2022), Artikel-ID 3498, Seite 1-14
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-022-07280-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: activation
• Sach-SW: arrays
• Sach-SW: differentiation
• Sach-SW: expression
• Sach-SW: growth
• Sach-SW: migration
• Sach-SW: phase reverse transfection
• Sach-SW: proliferation
• Sach-SW: signaling pathway
• Sach-SW: suppression
• K10plus-PPN: 1843062410
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

In response to vascular injury vascular smooth muscle cells (VSMCs) alternate between a differentiated (contractile) and a dedifferentiated (synthetic) state or phenotype. Although parts of the signaling cascade regulating the phenotypic switch have been described, the role of miRNAs is still incompletely understood. To systematically address this issue, we have established a microscopy-based quantitative assay and identified 23 miRNAs that induced contractile phenotypes when over-expressed. These were then correlated to miRNAs identified from RNA-sequencing when comparing cells in the contractile and synthetic states. Using both approaches, six miRNAs (miR-132-3p, miR-138-5p, miR-141-3p, miR-145-5p, miR-150-5p, and miR-22-3p) were filtered as candidates that induce the phenotypic switch from synthetic to contractile. To identify potentially common regulatory mechanisms of these six miRNAs, their predicted targets were compared with five miRNAs sharing ZBTB20, ZNF704, and EIF4EBP2 as common potential targets and four miRNAs sharing 16 common potential targets. The interaction network consisting of these 19 targets and additional 18 hub targets were created to facilitate validation of miRNA-mRNA interactions by suggesting the most plausible pairs. Furthermore, the information on drug candidates was integrated into the network to predict novel combinatorial therapies that encompass the complexity of miRNAs-mediated regulation. This is the first study that combines a phenotypic screening approach with RNA sequencing and bioinformatics to systematically identify miRNA-mediated pathways and to detect potential drug candidates to positively influence the phenotypic switch of VSMCs.