Evidence map›Paper›PMID 30354401›Full record

ArticleCirculation. Heart failure2018

Ufm1-Specific Ligase Ufl1 Regulates Endoplasmic Reticulum Homeostasis and Protects Against Heart Failure.

Jie Li, Guihua Yue, Wenxia Ma, Aizhen Zhang, Jianqiu Zou, Yafei Cai, Xiaoli Tang, Jun Wang, Jinbao Liu, Honglin Li and 1 more

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

Article in Circulation. Heart failure, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

56 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
  2. Ufl1-Mediated UFMylation Sustains Amelogenesis by Stabilizing RUNX2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  4. The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Jie LiVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Guihua YueVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Wenxia MaVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Aizhen ZhangVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Jianqiu ZouVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Yafei CaiCollege of Animal Science and Technology, Nanjing Agricultural University, China (Y.C.).
Xiaoli TangDepartment of Biochemistry, School of Medicine, Nanchang University, Jiangxi, China (X.T.).
Jun WangDepartment of Basic Research Laboratories, Center for Stem Cell Engineering, Texas Heart Institute, Houston (J.W.).
Jinbao LiuProtein Modification and Degradation Lab, School of Basic Medical Sciences, Guangzhou Medical University, China (J.L., H.S.).
Honglin LiDepartment of Biochemistry and Molecular Biology (H.L.), Medical College of Georgia, Augusta University.
Huabo SuVascular Biology Center (J.L., G.Y., W.M., A.Z., J.Z., H.S.), Medical College of Georgia, Augusta University.
Guangxi Medical University · CNNanchang University · CNNanjing Agricultural University · CN

Funding

Neddylation and cardiac protein quality controlR01HL124248 · NHLBI · AUGUSTA UNIVERSITY · PI SU, HUABO · 2014 to 2024
$4.1M
Essential role of the Ufm1 E3 ligase in intestinal homeostasisR01DK113409 · NIDDK · AUGUSTA UNIVERSITY · PI LI, HONGLIN · 2017 to 2020
$1.4M
NHLBI NIH HHS R01 HL124248NIDDK NIH HHS R01 DK113409
6 · The paper itself

Abstract

backgroundDefects in protein homeostasis are sufficient to provoke cardiac remodeling and dysfunction. Although posttranslational modifications by ubiquitin and ubiquitin-like proteins are emerging as an important regulatory mechanism of protein function, the role of Ufm1 (ubiquitin-fold modifier 1)-a novel ubiquitin-like protein-has not been explored in either the normal or stressed heart. METHODS AND

resultsWestern blotting revealed that Ufl1 (Ufm1-specific E3 ligase 1)-an enzyme essential for Ufm1 modification-was increased in hypertrophic mouse hearts but reduced in the failing hearts of patients with dilated cardiomyopathy. To determine the functional role of Ufl1 in the heart, we generated a cardiac-specific knockout mouse and showed that Ufl1-deficient mice developed age-dependent cardiomyopathy and heart failure, as indicated by elevated cardiac fetal gene expression, increased fibrosis, and impaired cardiac contractility. When challenged with pressure overload, Ufl1-deficient hearts exhibited remarkably greater hypertrophy, exacerbated fibrosis, and worsened cardiac contractility compared with control counterparts. Transcriptome analysis identified that genes associated with the endoplasmic reticulum (ER) function were dysregulated in Ufl1-deficient hearts. Biochemical analysis revealed that excessive ER stress preceded and deteriorated along with the development of cardiomyopathy in Ufl1-deficient hearts. Mechanistically, Ufl1 depletion impaired (PKR-like ER-resident kinase) signaling and aggravated cardiomyocyte cell death after ER stress. Administration of the chemical ER chaperone tauroursodeoxycholic acid to Ufl1-deficient mice alleviated ER stress and attenuated pressure overload-induced cardiac dysfunction.

conclusionsOur results advance a novel concept that the Ufm1 system is essential for cardiac homeostasis through regulation of ER function and that upregulation of myocardial Ufl1 could be protective against heart failure.

Indexed as

AnimalsEndoplasmic ReticulumEndoplasmic Reticulum StressHeart FailureHomeostasisHumansMice, KnockoutMyocardiumMyocytes, CardiacProtein Processing, Post-TranslationalProteinsProteinsUFM1 protein, humanendoplasmic reticulum stressheart failurehypertrophyubiquitin-like proteins

Identifiers

PMID30354401
PMCPMC6205741
OpenAlexW2896819099

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.