RGD Reference Report - MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells. - Rat Genome Database

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

Authors: Li, Chen Xi  Talele, Nilesh P  Boo, Stellar  Koehler, Anne  Knee-Walden, Ericka  Balestrini, Jenna L  Speight, Pam  Kapus, Andras  Hinz, Boris 
Citation: Li CX, etal., Nat Mater. 2017 Mar;16(3):379-389. doi: 10.1038/nmat4780. Epub 2016 Oct 31.
RGD ID: 41404703
Pubmed: (View Article at PubMed) PMID:27798620
DOI: Full-text: DOI:10.1038/nmat4780

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.

Annotation

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)


Additional Information