Blood-brain barrier (BBB) integrity is one of the important elements of central nervous system (CNS) homeostasis. MicroRNAs (miRs) have been demonstrated to play a role in many CNS disorders such as stroke and traumatic brain injury. MiR-212/132 are highly expressed in the CNS but their role at the BBB has not been characterized yet. Thus, we analyzed the expression of miR-212/132 in hypoxic mouse and human brain microvascular endothelial cells (BMEC) as well as in posttraumatic mouse and human brain tissue and serum exosomes. MiR-212/132 expression was detected in brain capillaries by in situ hybridization and was increased up to ten times in hypoxic BMEC. Over-expression of pre-miR-212/132 in BMEC decreased barrier properties and reduced migration of BMEC in the wound healing assay. We identified and validated tight junction proteins claudin-1 (Cldn1), junctional adhesion molecule 3 (Jam3), and tight junction-associated protein 1 (Tjap1) as potential miR-212/132 targets. Over-expression of miRs led to a decrease in mRNA and protein expression of Cldn1, Jam3, and Tjap1, which could be rescued by a respective anti-miR. In conclusion, our study identifies miR-212/132 as critical players at the hypoxic BBB. In addition, we propose three new direct miR-212/132 targets to be involved in miR-212/132-mediated effects on BBB properties.
Pubmed ID: 30617994 RIS Download
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An algorithm for the identification of microRNA targets. Details are provided (3' UTR alignments with predicted sites, links to various public databases etc) regarding: # microRNA target predictions in vertebrates (Krek et al, Nature Genetics 37:495-500 (2005)) # microRNA target predictions in seven Drosophila species (Grn et al, PLoS Comp. Biol. 1:e13 (2005)) # microRNA targets in three nematode species (Lall et al, Current Biology 16, 1-12 (2006)) # human microRNA targets that are not conserved but co-expressed (i.e. the microRNA and mRNA are expressed in the same tissue) (Chen and Rajewsky, Nat Genet 38, 1452-1456 (2006)) co-expressed targets
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