Evidence map›Paper›PMID 33438302›Full record

ArticleStem cells (Dayton, Ohio)2021

Intracellular matrix metalloproteinase-9 mediates epigenetic modifications and autophagy to regulate differentiation in human cardiac stem cells.

Santosh K Yadav, Paras K Mishra

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. MMP9Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  2. Article
  3. Article
  4. Improving iPSC Differentiation Using a Nanodot Platform.ACS applied materials & interfaces · 2024
    Article
  5. Article
  6. Review
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

2 authors at 1 institution in 1 country.

Santosh K YadavDepartment of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Paras K MishraDepartment of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.ORCID 0000-0002-7810-9239
University of Nebraska Medical Center · US

Funding

Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ZHANG, YING · 2016 to 2025
$42.8M
Inflammation, miRNA and autophagy in diabetesR01HL113281 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI MISHRA, PARAS KUMAR · 2013 to 2017
$1.9M
NHLBI NIH HHS R01 HL113281NIGMS NIH HHS U54 GM115458
6 · The paper itself

Abstract

Epigenetic reprogramming and autophagy have critical roles in differentiation of stem cells. However, very little is known about how epigenetic modifications are mediated and how they contribute to autophagy and differentiation in human cardiac stem cells (hCSCs). Previously, we have reported that intracellular matrix metalloproteinase-9 (MMP9), a collagenase, mediates cell death in hCSCs. Here, we investigated whether intracellular MMP9 mediates epigenetic modifications and autophagy in hCSCs. We created MMP9KO hCSCs and treated them with 5-azacytidine, an inhibitor of DNA methylation, and bafilomycin A1, an inhibitor of autophagosome degradation, and evaluated epigenetic modifications, autophagic flux, and differentiation. Our results showed compromised epigenetic modifications, reduced autophagy, and impaired differentiation in MMP9KO hCSCs. Remarkably, paracrine MMP9 supplementation restored epigenetic modifications but further reduced autophagy in MMP9KO hCSCs. We conclude that intracellular MMP9 is a critical mediator of epigenetic modifications and autophagy in hCSCs. Furthermore, the endocrine and paracrine effects of MMP9 vary for regulating autophagy in hCSCs. These novel roles of MMP9 are valuable for stem cell therapy.

Indexed as

Epigenesis, GeneticAutophagosomesAutophagyAzacitidineCell DifferentiationCRISPR-Cas SystemsDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationDNA Methyltransferase 3AGene DeletionHomeodomain ProteinsHumansMacrolidesMatrix Metalloproteinase 9MEF2 Transcription FactorsMyocytes, CardiacAzacitidinebafilomycin A1DNA (Cytosine-5-)-Methyltransferase 1DNA Methyltransferase 3ADNMT1 protein, humanDNMT3A protein, humanHomeodomain ProteinsMacrolidesMatrix Metalloproteinase 9MEF2C protein, humanMEF2 Transcription FactorsMKX protein, humanMMP9 protein, humanSIRT1 protein, humanSirtuin 15-azacytidineautophagic fluxCRISPR-Cas9differentiationDNMTmigrationMMPmTORproliferation

Identifiers

PMID33438302
PMCPMC9188476
OpenAlexW3119542800

What OpenQuestion holds

Textmetadata
LicenceTDM
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.