Hypoxia Alters MicroRNA Expression in Rat Cortical Pericytes
2013
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
57
References
33
Citations
NaN
KQI