Evidence map›Paper›PMID 27798620›Full record

ArticleNature materials2017

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

Chen Xi Li, Nilesh P Talele, Stellar Boo, Anne Koehler, Ericka Knee-Walden, Jenna L Balestrini, Pam Speight, Andras Kapus, Boris Hinz

Abstract read
PubMed Publisher
In one paragraph

Article in Nature materials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers.

0numbers the graph read from it
0cells of the map it votes in
209citing papers in PubMed
14.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

209 citing papers in PubMed, 321 citations in OpenAlex.

  1. Article
  2. Mechanical regulation of cell memory.Nature structural & molecular biology · 2026
    Review
  3. Article
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  5. RUNX1 is a mediator of fibrotic activation and epigenetic memory in lung fibroblasts.American journal of respiratory cell and molecular biology · 2026
    Article
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149 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Chen Xi LiLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Nilesh P TaleleLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.ORCID 0000-0003-2758-8599
Stellar BooLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Anne KoehlerLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Ericka Knee-WaldenLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Jenna L BalestriniDraper, Cambridge, Massachusetts 02139, USA.
Pam SpeightKeenan Research Centre in the Li Ka Shing Knowledge Institute in the St. Michael's Hospital, and Department of Surgery, University of Toronto, Toronto, Ontario M5B 1W8, Canada.
Andras KapusKeenan Research Centre in the Li Ka Shing Knowledge Institute in the St. Michael's Hospital, and Department of Surgery, University of Toronto, Toronto, Ontario M5B 1W8, Canada.
Boris HinzLaboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5S 3E2, Canada.ORCID 0000-0002-0526-393X
University of Toronto · CASt. Michael's Hospital · CADraper Laboratory · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Stress, MechanicalAnimalsFibrosisMesenchymal Stem CellsMicroRNAsRatsRats, WistarTranscription FactorsMicroRNAsmirn21 microRNA, ratmyocardin-related transcription factor-A, ratTranscription Factors

Identifiers

PMID27798620
OpenAlexW2539719512

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.