Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar;16(3):379-389.
doi: 10.1038/nmat4780. Epub 2016 Oct 31.

MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells

Affiliations

MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells

Chen Xi Li et al. Nat Mater. 2017 Mar.

Abstract

Expansion on stiff culture substrates activates pro-fibrotic cell programs that are retained by mechanical memory. Here, we show that priming on physiologically soft silicone substrates suppresses fibrogenesis and desensitizes mesenchymal stem cells (MSCs) against subsequent mechanical activation in vitro and in vivo, and identify the microRNA miR-21 as a long-term memory keeper of the fibrogenic program in MSCs. During stiff priming, miR-21 levels were gradually increased by continued regulation through the acutely mechanosensitive myocardin-related transcription factor-A (MRTF-A/MLK-1) and remained high over 2 weeks after removal of the mechanical stimulus. Knocking down miR-21 once by the end of the stiff-priming period was sufficient to erase the mechanical memory and sensitize MSCs to subsequent exposure to soft substrates. Soft priming and erasing mechanical memory following cell culture expansion protects MSCs from fibrogenesis in the host wound environment and increases the chances for success of MSC therapy in tissue-repair applications.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Clin Invest. 2013 Mar;123(3):1096-108 - PubMed
    1. Circulation. 2012 Aug 14;126(7):800-2 - PubMed
    1. Nat Rev Mol Cell Biol. 2002 May;3(5):349-63 - PubMed
    1. Nat Rev Mol Cell Biol. 2012 Sep;13(9):591-600 - PubMed
    1. Periodontol 2000. 2013 Oct;63(1):14-28 - PubMed

Publication types

Substances

LinkOut - more resources