Evidence map›Paper›PMID 31515484›Full record

ArticleCell death & disease2019

Activation of TFEB ameliorates dedifferentiation of arterial smooth muscle cells and neointima formation in mice with high-fat diet.

Yun-Ting Wang, Xiang Li, Jiajie Chen, Bradley K McConnell, Li Chen, Pin-Lan Li, Yang Chen, Yang Zhang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

23 citing papers in PubMed, 40 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Yun-Ting WangSchool of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China.
Xiang LiDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
Jiajie ChenDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
Bradley K McConnellDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
Li ChenDepartment of Biology and Biochemistry, University of Houston, Houston, TX, USA.
Pin-Lan LiDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Yang ChenSchool of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China. ychen8@gzucm.edu.cn.
Yang ZhangDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA. yzhan219@central.uh.edu.
University of Houston · USGuangzhou University of Chinese Medicine · CNVirginia Commonwealth University · US

Funding

Regulation of Lysosomes in Autophagy in Coronary Arterial MyocytesR01HL057244 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2001 to 2021
$6.7M
Subendothelial Exosomes in Coronary Microvascular DysfunctionR01HL075316 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2004 to 2024
$6.7M
Lysosome Trafficking Dysregulation of Arterial Myocytes in AtherogenesisR01HL122937 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN, ZHANG, YANG · 2014 to 2024
$4.0M
Endothelial Inflammasomes in Coronary Microcirculation -Beyond InflammationR01HL122769 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YANG · 2014 to 2018
$1.9M
Gravin Signalosome Protein Coordinates Cardiac Function via Adrenergic Receptor SignalingR15HL141963 · NHLBI · UNIVERSITY OF HOUSTON · PI MCCONNELL, BRADLEY K · 2019 to 2019
$459k
NHLBI NIH HHS R01 HL057244NHLBI NIH HHS R01 HL075316NHLBI NIH HHS R01 HL122769NHLBI NIH HHS R01 HL122937NHLBI NIH HHS R15 HL141963
6 · The paper itself

Abstract

Autophagy is recently implicated in regulating vascular smooth muscle cell (SMC) homeostasis and in the pathogenesis of vascular remodeling. Transcription factor EB (TFEB) is a master regulator of autophagy signaling pathways. However, the molecular mechanisms and functional roles of TFEB in SMC homeostasis have not been elucidated. Here, we surveyed the ability of TFEB to regulate autophagy pathway in SMCs, and whether pharmacological activation of TFEB favors SMC homeostasis preventing dedifferentiation and pathogenic vascular remodeling. In primary cultured SMCs, TFEB activator trehalose induced nuclear translocation of TFEB and upregulation of TFEB-controlled autophagy genes leading to enhanced autophagy signaling. Moreover, trehalose suppressed serum-induced SMC dedifferentiation to synthetic phenotypes as characterized by inhibited proliferation and migration. These effects of trehalose were mimicked by ectopic upregulation of TFEB and inhibited by TFEB gene silencing. In animal experiments, partial ligation of carotid arteries induced downregulation of TFEB pathway in the media layer of these arteries. Such TFEB suppression was correlated with increased SMC dedifferentiation and aggravated high-fat diet (HFD)-induced neointima formation. Treatment of mice with trehalose reversed this TFEB pathway suppression, and prevented SMC dedifferentiation and HFD-induced neointima formation. In conclusion, our findings have identified TFEB as a novel positive regulator for autophagy pathway and cellular homeostasis in SMCs. Our data suggest that suppression of TFEB may be an initiating mechanism that promotes SMC dedifferentiation leading to accelerated neointima formation in vascular disorders associated with metabolic stress, whereas trehalose reverses these changes. These findings warrant further evaluation of trehalose in the clinical settings.

Indexed as

AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell MovementCell ProliferationCells, CulturedDiet, High-FatFluorescent Antibody TechniqueMaleMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaReal-Time Polymerase Chain ReactionSignal TransductionBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsTcfeb protein, mouse

Identifiers

PMID31515484
PMCPMC6742653
OpenAlexW2973101125

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.