RGD Reference Report - Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. - Rat Genome Database

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Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

Authors: Ungvari, Zoltan  Tucsek, Zsuzsanna  Sosnowska, Danuta  Toth, Peter  Gautam, Tripti  Podlutsky, Andrej  Csiszar, Agnes  Losonczy, Gyorgy  Valcarcel-Ares, M Noa  Sonntag, William E  Csiszar, Anna 
Citation: Ungvari Z, etal., J Gerontol A Biol Sci Med Sci. 2013 Aug;68(8):877-91. doi: 10.1093/gerona/gls242. Epub 2012 Dec 13.
RGD ID: 149735901
Pubmed: PMID:23239824   (View Abstract at PubMed)
PMCID: PMC3712357   (View Article at PubMed Central)
DOI: DOI:10.1093/gerona/gls242   (Journal Full-text)

Age-related impairment of angiogenesis is likely to play a central role in cerebromicrovascular rarefaction and development of vascular cognitive impairment, but the underlying mechanisms remain elusive. To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in aging, primary cerebromicrovascular endothelial cells (CMVECs) were isolated from young (3 months old) and aged (24 months old) Fischer 344 × Brown Norway rats. We found an age-related downregulation of Dicer1 expression both in CMVECs and in small cerebral vessels isolated from aged rats. In aged CMVECs, Dicer1 expression was increased by treatment with polyethylene glycol-catalase. Compared with young cells, aged CMVECs exhibited altered miRNA expression profile, which was associated with impaired proliferation, adhesion to vitronectin, collagen and fibronectin, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing technology), and impaired ability to form capillary-like structures. Overexpression of Dicer1 in aged CMVECs partially restored miRNA expression profile and significantly improved angiogenic processes. In young CMVECs, downregulation of Dicer1 (siRNA) resulted in altered miRNA expression profile associated with impaired proliferation, adhesion, migration, and tube formation, mimicking the aging phenotype. Collectively, we found that Dicer1 is essential for normal endothelial angiogenic processes, suggesting that age-related dysregulation of Dicer1-dependent miRNA expression may be a potential mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging.

Gene Ontology Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Dicer1  (dicer 1 ribonuclease III)


Additional Information