Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Perinatal Whole Blood Zinc Status and Cytokines, Adipokines, and Other Immune Response Proteins

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Bone turnover markers in children and adolescents with type 1 diabetes-A systematic review

    Research output: Contribution to journalReviewResearchpeer-review

  3. Tu1766 – Dysregulated Lncrnas in Inflammatory Bowel Disease Demonstrate Immune System Related Association Through Guilt-By Association Analysis

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  4. Cathepsin C and D regulate cytokine-induced beta-cell death

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

View graph of relations

Endothelial dysfunction is a key element in cerebral small vessel disease (CSVD), which may cause stroke and cognitive decline. Cyclic nucleotide signaling modulates endothelial function. The cyclic adenosine monophosphate-degrading enzyme phosphodiesterase 3 (PDE3) is an important treatment target which may be modulated by microRNAs (miRNAs) important for regulating gene expression. We aimed to identify PDE3-targeting miRNAs to highlight potential therapeutic targets for endothelial dysfunction and CSVD. PDE3-targeting miRNAs were identified by in silico analysis (TargetScan, miRWalk, miRanda, and RNA22). The identified miRNAs were ranked on the basis of TargetScan context scores and their expression (log2 read counts) in a human brain endothelial cell line (hCMEC/D3) described recently. miRNAs were subjected to co-expression meta-analysis (CoMeTa) to create miRNA clusters. The pathways targeted by the miRNAs were assigned functional annotations via the KEGG pathway and COOL. hCMEC/D3 cells were transfected with miRNA mimics miR-27a-3p and miR-222-3p, and the effect on PDE3A protein expression was analyzed by Western blotting. Only PDE3A is expressed in hCMEC/D3 cells. The in silico prediction identified 67 PDE3A-related miRNAs, of which 49 were expressed in hCMEC/D3 cells. Further analysis of the top two miRNA clusters (miR-221/miR-222 and miR-27a/miR-27b/miR-128) indicated a potential link to pathways relevant to cerebral and vascular integrity and repair. hCMEC/D3 cells transfected with miR-27a-3p and miR-222-3p mimics had reduced relative expression of PDE3A protein. PDE3A-related miRNAs miR-221/miR-222 and miR-27a/miR-27b/miR-128 are potentially linked to pathways essential for immune regulation as well as cerebral and vascular integrity/function. Furthermore, relative PDE3A protein expression was reduced by miR27a-3p and miR-222-3p.

Original languageEnglish
JournalMolecular Neurobiology
Volume56
Issue number8
Pages (from-to)5304-5314
Number of pages11
ISSN0893-7648
DOIs
Publication statusPublished - 15 Aug 2019

    Research areas

  • Endothelial cells, PDE3, Small vessel disease, Stroke, microRNA

ID: 56067792