Evidence map›Paper›PMID 25789971›Full record

ArticleCell death & disease2015

Autophagy is a regulator of TGF-β1-induced fibrogenesis in primary human atrial myofibroblasts.

S Ghavami, R H Cunnington, S Gupta, B Yeganeh, K L Filomeno, D H Freed, S Chen, T Klonisch, A J Halayko, E Ambrose and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 1 pooled it
14.0field-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

124 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.

  1. The Role of microRNAs in Heart Failure: A Systematic Review.Frontiers in cardiovascular medicine · 2020
    Pooled it
  2. Review
  3. Article
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  5. Article
  6. Article
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  8. Article
  9. Alpha-Actinin-3 Deficiency Links Genetic Susceptibility to Renal Fibrosis: Evidence From Hemodialysis Patients and Murine Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  10. Article
  11. Article
  12. Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
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  19. Article
  20. Review

64 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

12 authors at 4 institutions in 1 country.

S Ghavami1] Department of Physiology, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [2] Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [3] Department of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada [4] Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
R H CunningtonDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
S GuptaDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
B Yeganeh1] Department of Physiology, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [2] Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [3] Department of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
K L FilomenoDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
D H FreedDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
S ChenDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
T KlonischDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
A J Halayko1] Department of Physiology, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [2] Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada [3] Department of Internal Medicine, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
E AmbroseDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
R SingalCardiac Sciences Program, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
I M C DixonDepartment of Physiology and Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
University of Manitoba · CAChildren's Hospital Research Institute of Manitoba · CAResearch Manitoba · CASt. Boniface Hospital · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Transforming growth factor-β(1) (TGF-β(1)) is an important regulator of fibrogenesis in heart disease. In many other cellular systems, TGF-β(1) may also induce autophagy, but a link between its fibrogenic and autophagic effects is unknown. Thus we tested whether or not TGF-β(1)-induced autophagy has a regulatory function on fibrosis in human atrial myofibroblasts (hATMyofbs). Primary hATMyofbs were treated with TGF-β(1) to assess for fibrogenic and autophagic responses. Using immunoblotting, immunofluorescence and transmission electron microscopic analyses, we found that TGF-β(1) promoted collagen type Iα2 and fibronectin synthesis in hATMyofbs and that this was paralleled by an increase in autophagic activation in these cells. Pharmacological inhibition of autophagy by bafilomycin-A1 and 3-methyladenine decreased the fibrotic response in hATMyofb cells. ATG7 knockdown in hATMyofbs and ATG5 knockout (mouse embryonic fibroblast) fibroblasts decreased the fibrotic effect of TGF-β(1) in experimental versus control cells. Furthermore, using a coronary artery ligation model of myocardial infarction in rats, we observed increases in the levels of protein markers of fibrosis, autophagy and Smad2 phosphorylation in whole scar tissue lysates. Immunohistochemistry for LC3β indicated the localization of punctate LC3β with vimentin (a mesenchymal-derived cell marker), ED-A fibronectin and phosphorylated Smad2. These results support the hypothesis that TGF-β(1)-induced autophagy is required for the fibrogenic response in hATMyofbs.

Indexed as

AdenineAnimalsAutophagyAutophagy-Related Protein 5Autophagy-Related Protein 7Cell ProliferationCollagen Type IFibronectinsFibrosisHeart AtriaHumansMacrolidesMiceMicrotubule-Associated ProteinsMyofibroblastsPrimary Cell Culture3-methyladenineAdenineAtg5 protein, mouseAtg7 protein, mouseAutophagy-Related Protein 5Autophagy-Related Protein 7bafilomycin A1Collagen Type IFibronectinsMacrolidesMicrotubule-Associated ProteinsSmad2 ProteinSMAD2 protein, humanTGFB1 protein, humanTransforming Growth Factor beta1

Identifiers

PMID25789971
PMCPMC4385916
OpenAlexW2093295909

What OpenQuestion 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 OpenQuestion graph.