Evidence map›Paper›PMID 30643122›Full record

ArticleNature communications2019

Pharmacologic ATF6 activation confers global protection in widespread disease models by reprograming cellular proteostasis.

Erik A Blackwood, Khalid Azizi, Donna J Thuerauf, Ryan J Paxman, Lars Plate, Jeffery W Kelly, R Luke Wiseman, Christopher C Glembotski

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
13.5field-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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  5. Article
  6. Review
  7. International journal of molecular sciences · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. ATF6 enables pathogen infection in ticks by inducingProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

62 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

8 authors at 2 institutions in 1 country.

Erik A BlackwoodSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, 92182, USA.
Khalid AziziSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, 92182, USA.
Donna J ThueraufSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, 92182, USA.
Ryan J PaxmanDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Lars PlateDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Jeffery W KellyDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
R Luke WisemanDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0001-9287-6840
Christopher C GlembotskiSan Diego State University Heart Institute and the Department of Biology, San Diego State University, San Diego, CA, 92182, USA. cglembotski@sdsu.edu.
San Diego State University · USScripps Research Institute · US

Funding

Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
Surgery, Physiology and ImmunohistopathologyP01HL085577 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GUSTAFSSON, ASA B. · 2006 to 2017
$18.4M
Discovering small molecules activators of stress responsive signalingR01AG046495 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI JEFFERY W KELLY, Rockland Luke Wiseman · 2013 to 2026
$6.0M
Establishing Strategies to Ameliorate Amyloid Pathology in Light Chain AmyloidosisR01DK107604 · NIDDK · SCRIPPS RESEARCH INSTITUTE, THE · PI WISEMAN, ROCKLAND LUKE · 2016 to 2024
$4.3M
Role of Unfolded Protein Response in Cardiac ProtectionR01HL075573 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GLEMBOTSKI, CHRIS · 2004 to 2011
$3.0M
Direct Regulation of Extracellular Proteostasis by the Unfolded Protein ResponseR01NS092829 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI WISEMAN, ROCKLAND LUKE · 2015 to 2019
$2.1M
Role of the SR/ER E3 Ubiquitin Ligase Synoviolin 1 in Cardiac HypertrophyR01HL127439 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GLEMBOTSKI, CHRIS · 2015 to 2018
$1.7M
The ER Stress-Induced Selenoprotein, SelenoS, Regulates Proteostasis and Cardiac HypertrophyR01HL149931 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2020 to 2023
$1.7M
Harnessing the Adaptive ER Stress Response in Myocardial IschemiaR01HL135893 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2017 to 2020
$1.5M
ATF6 is Required for ANP Secretion from the HeartR01HL141463 · NHLBI · UNIVERSITY OF ARIZONA · PI GLEMBOTSKI, CHRIS · 2019 to 2022
$1.5M
Roles for ER Stress Inducible Cardiomyokines in the heartR01HL104535 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GLEMBOTSKI, CHRIS · 2010 to 2013
$1.5M
TARGETING ENDOGENOUS SIGNALING PATHWAYS TO AMELIORATE SYSTEMIC AMYLOIDOSESR01DK102635 · NIDDK · SCRIPPS RESEARCH INSTITUTE, THE · PI MURPHY, GEORGE J, WISEMAN, ROCKLAND LUKE · 2014 to 2017
$823k
NCATS NIH HHS UL1 TR001114NHLBI NIH HHS P01 HL085577NHLBI NIH HHS R01 HL075573NHLBI NIH HHS R01 HL104535NHLBI NIH HHS R01 HL127439NHLBI NIH HHS R01 HL135893NHLBI NIH HHS R01 HL141463NHLBI NIH HHS R01 HL149931NIA NIH HHS R01 AG046495NIDDK NIH HHS R01 DK102635NIDDK NIH HHS R01 DK107604NINDS NIH HHS R01 NS092829NINDS NIH HHS R21 NS079882
6 · The paper itself

Abstract

Pharmacologic activation of stress-responsive signaling pathways provides a promising approach for ameliorating imbalances in proteostasis associated with diverse diseases. However, this approach has not been employed in vivo. Here we show, using a mouse model of myocardial ischemia/reperfusion, that selective pharmacologic activation of the ATF6 arm of the unfolded protein response (UPR) during reperfusion, a typical clinical intervention point after myocardial infarction, transcriptionally reprograms proteostasis, ameliorates damage and preserves heart function. These effects were lost upon cardiac myocyte-specific Atf6 deletion in the heart, demonstrating the critical role played by ATF6 in mediating pharmacologically activated proteostasis-based protection of the heart. Pharmacological activation of ATF6 is also protective in renal and cerebral ischemia/reperfusion models, demonstrating its widespread utility. Thus, pharmacologic activation of ATF6 represents a proteostasis-based therapeutic strategy for ameliorating ischemia/reperfusion damage, underscoring its unique translational potential for treating a wide range of pathologies caused by imbalanced proteostasis.

Indexed as

Activating Transcription Factor 6AnimalsAnimals, NewbornCells, CulturedCerebral InfarctionDisease Models, AnimalEndoplasmic ReticulumFemaleHeart VentriclesHumansKidneyKidney DiseasesMaleMiceMice, Inbred C57BLMice, KnockoutActivating Transcription Factor 6Atf6 protein, mouseProtective Agents

Identifiers

PMID30643122
PMCPMC6331617
OpenAlexW2908615024

What OpenQuestion holds

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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.