Evidence map›Paper›PMID 25549087›Full record

Trial reportPloS one2014

MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-β activated kinase 1 binding protein 1, implications for systemic sclerosis.

Marzena Ciechomska, Steven O'Reilly, Monika Suwara, Katarzyna Bogunia-Kubik, Jacob M van Laar

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
5.9field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.

  1. Pooled it
  2. A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2017
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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

5 authors at 2 institutions in 3 countries.

Marzena CiechomskaNewcastle University, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, United Kingdom; L. Hirszferd Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
Steven O'ReillyNewcastle University, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, United Kingdom.
Monika SuwaraNewcastle University, Fibrosis Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, United Kingdom.
Katarzyna Bogunia-KubikL. Hirszferd Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
Jacob M van LaarNewcastle University, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, United Kingdom; University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, the Netherlands.
Newcastle University · GBLudwik Hirszfeld Institute of Immunology and Experimental Therapy · PL

Funding

Department of Health
6 · The paper itself

Abstract

backgroundSystemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by skin and internal organs fibrosis due to accumulation of extra cellular matrix (ECM) proteins. Tissue inhibitor of metalloproteinases 1 (TIMP-1) plays a key role in ECM deposition.

aimTo investigate the role of miR-29a in regulation of TAB1-mediated TIMP-1 production in dermal fibroblasts in systemic sclerosis.

methodsHealthy control (HC) and SSc fibroblasts were cultured from skin biopsies. The expression of TIMP-1, MMP-1 and TGF-β activated kinase 1 binding protein 1 (TAB1) was measured following miR-29a transfection using ELISA, qRT-PCR, and Western Blotting. The functional effect of miR-29a on dermal fibroblasts was assessed in collagen gel assay. In addition, HeLa cells were transfected with 3'UTR of TAB1 plasmid cloned downstream of firefly luciferase gene to assess TAB1 activity. HC fibroblasts and HeLa cells were also transfected with Target protectors in order to block the endogenous miR-29a activity.

resultsWe found that TAB1 is a novel target gene of miR-29a, also regulating downstream TIMP-1 production. TAB1 is involved in TGF-β signal transduction, a key cytokine triggering TIMP-1 production. To confirm that TAB1 is a bona fide target gene of miR-29a, we used a TAB1 3'UTR luciferase assay and Target protector system. We showed that miR-29a not only reduced TIMP-1 secretion via TAB1 repression, but also increased functional MMP-1 production resulting in collagen degradation. Blocking TAB1 activity by pharmacological inhibition or TAB1 knockdown resulted in TIMP-1 reduction, confirming TAB1-dependent TIMP-1 regulation. Enhanced expression of miR-29a was able to reverse the profibrotic phenotype of SSc fibroblasts via downregulation of collagen and TIMP-1.

conclusionsmiR-29a repressed TAB1-mediated TIMP-1 production in dermal fibroblasts, demonstrating that miR-29a may be a therapeutic target in SSc.

Indexed as

3' Untranslated RegionsAdaptor Proteins, Signal TransducingDermisExtracellular Matrix ProteinsFemaleFibroblastsGene Expression RegulationHeLa CellsHumansMaleMicroRNAsProteolysisScleroderma, SystemicTissue Inhibitor of Metalloproteinase-13' Untranslated RegionsAdaptor Proteins, Signal TransducingExtracellular Matrix ProteinsMicroRNAsMIRN29a microRNA, humanTAB1 protein, humanTIMP1 protein, humanTissue Inhibitor of Metalloproteinase-1

Identifiers

PMID25549087
PMCPMC4280195
OpenAlexW2050759685

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.