title: miR-486-5p induces replicative senescence of human adipose tissue-derived mesenchymal stem cells and its expression is controlled by high glucose.
abstract: The reduction of adult stem cell self-renewal can be an important mechanism of aging. MicroRNAs have been reported to be involved in aging processes. Through a microarray approach, we have identified miR-486-5p, the expression of which is progressively expressed in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) with aging. Overexpression of miR-486-5p induces a premature senescence-like phenotype and inhibits proliferation of hAT-MSCs and inhibits adipogenic and osteogenic differentiation, whereas inhibition of miR-486-5p has the opposite effects. miR-486-5p regulates the expression of silent information regulator 1 (SIRT1), a major regulator of longevity and metabolic disorders. Decrease of SIRT1 deacetylase activity in hAT-MSCs is correlated with their passage number. miR-486-5p inhibits SIRT1 expression through a miR-486-5p binding site within the 3'-untranslated region of SIRT1. Overexpression of miR-486-5p inhibits SIRT1 deacetylase activity in hAT-MSCs, and transfection of miR-486-5p inhibitor shows the opposite effect. Downregulation of SIRT1 in hAT-MSCs induces senescence and inhibits cell proliferation. Exposure to high glucose increases miR-486-5p expression and inhibits SIRT1 expression in hAT-MSCs. Our data pinpoint miR-486-5p as an endogenous inhibitor of SIRT1 that promotes hAT-MSCs senescence and is potentially applicable to therapeutic manipulation of hAT-MSCs dysfunction in metabolic disorders.
authors: Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Korea.
authors: Yeon Jeong
authors: YJ
authors: Kim
authors: Soo Hyun
authors: SH
authors: Hwang
authors: Sun Young
authors: SY
authors: Lee
authors: Keun Koo
authors: KK
authors: Shin
authors: Hyun Hwa
authors: HH
authors: Cho
authors: Yong Chan
authors: YC
authors: Bae
authors: Jin Sup
authors: JS
authors: Jung
mesh_terms: D020413:3' Untranslated Regions; D050153:Abdominal Fat / Q000166:cytology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C560945:MIRN486 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C061901:GLB1 protein, human; D001616:beta-Galactosidase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose