title: Hypoxia alters MicroRNA expression in rat cortical pericytes.
abstract: Microvascular adaptation to metabolic stress is important in the maintenance of tissue homeostasis. Nowhere is this more important than in the central nervous system (CNS) where the cellular constituents of the neurovascularture including endothelial cells, pericytes and some astroglia must make fine-tuned autoregulatory modulations that maintain the delicate balance between oxygen availability and metabolic demand. miRNAs have been reported to play an important regulatory role in many cellular functions including cell differentiation, growth and proliferation, lineage determination, and metabolism. In this study, we investigated the possible role of miRNAs in the CNS capillary pericyte response to hypoxic stress. Micro-array analysis was used to examine the expression of 388 rat miRNAs in primary rat cortical pericytes with and without exposure to low oxygen (1%) after 24 or 48 hr. Pericytes subjected to hypoxia showed 27 miRNAs that were higher than control and 31 that were lower. Validation and quantification was performed by Real Time RT-PCR on pericytes subjected to 2 hr, 24 hr, or 48 hr of hypoxia. Hypoxia induced changes included physiological pathways governing the stress response, angiogenesis, migration and cell cycle regulation. miRNAs associated with HIF-1α (miR-322[1], miR-199a [2]), TGF-β1 (miR-140[3], miR-145[4], miR-376b-3p[5]) and VEGF (miR-126a[6], miR-297[7], miR-16[8], miR-17-5p[9]) were differentially regulated. Systematic and integrative analysis of possible gene targets analyzed by DAVID bioinformatics resource (http://david.abcc.ncifcrf.gov) and MetaSearch 2.0 (GeneGo) for some of these miRNAs was conducted to determine possible gene targets and pathways that may be affected by the post-transcriptional changes after hypoxic insult.
authors.affiliation: Dept of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Fl. USA.
authors.forename: Jessie S
authors.initials: JS
authors.lastname: Truettner
authors.affiliation: Dept of Neurology Wayne State University School of Medicine, Detroit, Mi, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Katyshev
authors.affiliation: Dept of Neurology Wayne State University School of Medicine, Detroit, Mi, USA.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen-Bilgin
authors.affiliation: Dept of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Fl. USA.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.affiliation: Dept of Neurology Wayne State University School of Medicine, Detroit, Mi, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Dore-Duffy
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019295:Computational Biology; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055806:Microvessels / Q000166:cytology; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A
keywords: Brain; hypoxia; microRNA; microvasculature; pericyte; posttranscriptional regulation; translational repression