Evidence map›Paper›PMID 40261911›Full record

ArticlePLoS biology2025

Werner syndrome exonuclease promotes gut regeneration and causes age-associated gut hyperplasia in Drosophila.

Kun Wu, Juanyu Zhou, Yiming Tang, Qiaoqiao Zhang, Lishou Xiong, Xiaorong Li, Zhangpeng Zhuo, Mei Luo, Yu Yuan, Xingzhu Liu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Kun WuWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Juanyu ZhouWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Yiming TangWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Qiaoqiao ZhangWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Lishou XiongDepartment of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Xiaorong LiSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, China.
Zhangpeng ZhuoKey Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
Mei LuoDepartment of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yu YuanWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Xingzhu LiuWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Zhendong ZhongKey Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
XiaoXin GuoWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Zihua YuWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Xiao ShengWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Guanzheng LuoKey Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
Haiyang ChenWest China Centre of Excellence for Pancreatitis and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.ORCID https://orcid.org/0000-0001-8305-4060

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human Werner syndrome (adult progeria, a well-established model of human aging) is caused by mutations in the Werner syndrome (WRN) gene. However, the expression patterns and functions of WRN in natural aging remain poorly understood. Despite the link between WRN deficiencies and progeria, our analyses of human colon tissues, mouse crypts, and Drosophila midguts revealed that WRN expression does not decrease but rather increases in intestinal stem cells (ISCs) with aging. Mechanistically, we found that the Drosophila WRN homologue (WRNexo) binds to Heat shock 70-kDa protein cognate 3 (Hsc70-3/Bip) to regulate the unfolded protein response of the endoplasmic reticulum (UPRER). Activation of the WRNexo-mediated UPRER in ISCs is required for ISC proliferation during injury repair. However, persistent DNA damage during aging leads to chronic upregulation of WRNexo in ISCs, where excessive WRNexo-induced ER stress drives age-associated gut hyperplasia in Drosophila. This study reveals how elevated WRNexo contributes to stem cell aging, providing new insights into organ aging and the pathogenesis of age-related diseases, such as colon cancer.

Indexed as

AgingDrosophila ProteinsRegenerationWerner SyndromeWerner Syndrome HelicaseAnimalsDNA DamageDrosophilaDrosophila melanogasterEndoplasmic Reticulum StressHumansHyperplasiaIntestinesMiceStem CellsUnfolded Protein ResponseDrosophila ProteinsWerner Syndrome Helicase

Identifiers

PMID40261911
PMCPMC12013949

What OpenQuestion holds

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Registered trials

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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.