miR-23a-3p causes cellular senescence by targeting hyaluronan synthase2: Possible implication for skin aging.
J. Invest. Dermatol. 135, 369-377 (2014)
Even though aging and cellular senescence appear to be linked the biological mechanisms interconnecting these two processes remain to be unravelled. Therefore, miRNA profiles were analyzed ex vivo by gene array in fibroblasts isolated from young and old human donors. Expression of several miRNAs was positively correlated with donor age. Among those miR-23a-3p was shown to target hyaluronan-synthase 2. Hyaluronan (HA) is a polysaccharide of the extracellular matrix that critically regulates the phenotype of fibroblasts. Indeed, both aged and senescent fibroblasts showed increased miR-23a-3p expression and secreted significantly lower amounts of HA compared to young and non senescent fibroblasts. Ectopic overexpression of miR-23a-3p in non senescent fibroblasts led to decreased HAS2 mediated HA-synthesis, upregulation of senescence associated markers and decreased proliferation. In addition, siRNA mediated downregulation of HAS2 and pharmacologic inhibition of HA-synthesis by 4-methylumbelliferone mimicked the effects of miR-23a-3p. In vivo, miR-23a-3p was upregulated and HAS2 was downregulated in the skin of old mice versus young mice. Inhibition of HA-synthesis by 4-methylumbelliferone in mice reduced dermal hydration and viscoelasticity thereby mimicking an aged skin phenotype. Taken together, these findings appear to link miR-23a-3p and the HA-microenvironment as effector mechanisms in both dermal aging and senescence.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Life-span; Microrna Expression; Growth Arrest; Cells; Fibroblasts; Metabolism; Stem; Matrix; Irradiation; P16(ink4a)
ISSN (print) / ISBN 0022-202X
Zeitschrift Journal of Investigative Dermatology, The
Quellenangaben Band: 135, Heft: 2, Seiten: 369-377
Verlagsort New York, NY
Institut(e) Institute of Computational Biology (ICB)