1. miR-486-5p Induces Replicative Senescence of Human Adipose Tissue-Derived Mesenchymal Stem Cells and Its Expression Is Controlled by High Glucose
- Author
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Sun-Young Lee, Yeon Jeong Kim, Hyun Hwa Cho, Keun Koo Shin, Yong Chan Bae, Jin Sup Jung, and Soo Hyun Hwang
- Subjects
Senescence ,Abdominal Fat ,Adipose tissue ,Endogeny ,Biology ,environment and public health ,Sirtuin 1 ,Downregulation and upregulation ,parasitic diseases ,Humans ,RNA, Messenger ,3' Untranslated Regions ,Cells, Cultured ,Cellular Senescence ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Gene Expression Profiling ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,Hematology ,beta-Galactosidase ,Cell biology ,MicroRNAs ,enzymes and coenzymes (carbohydrates) ,Glucose ,Gene Expression Regulation ,RNA Interference ,Developmental Biology ,Adult stem cell ,Deacetylase activity - 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.
- Published
- 2012