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J Cell Sci. 2013 Dec 1;126(Pt 23):5422-31. doi: 10.1242/jcs.133314. Epub 2013 Oct 7.

MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly targeting ZMPSTE24.

Author information

1
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea.

Erratum in

  • J Cell Sci. 2014 Jan 15;127(Pt 2):475.

Abstract

Human mesenchymal stem cell (hMSC) aging may lead to a reduced tissue regeneration capacity and a decline in physiological functions. However, the molecular mechanisms controlling hMSC aging in the context of prelamin A accumulation are not completely understood. In this study, we demonstrate that the accumulation of prelamin A in the nuclear envelope results in cellular senescence and potential downstream regulatory mechanisms responsible for prelamin A accumulation in hMSCs. We show for the first time that ZMPSTE24, which is involved in the post-translational maturation of lamin A, is largely responsible for the prelamin A accumulation related to cellular senescence in hMSCs. Direct binding of miR-141-3p to the 3'UTR of ZMPSTE24 transcripts was confirmed using a 3'UTR-luciferase reporter assay. We also found that miR-141-3p, which is overexpressed during senescence as a result of epigenetic regulation, is able to decrease ZMPSTE24 expression levels, and leads to an upregulation of prelamin A in hMSCs. This study provides new insights into mechanisms regulating MSC aging and may have implications for therapeutic application to reduce age-associated MSC pool exhaustion.

KEYWORDS:

Aging; Histone modification; Mesenchymal stem cells; Prelamin A accumulation; ZMPSTE24; miRNA-141-3p

PMID:
24101728
DOI:
10.1242/jcs.133314
[Indexed for MEDLINE]
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