Evidence map›Paper›PMID 27996033›Full record

ArticleScientific reports2016

The XBP1 Arm of the Unfolded Protein Response Induces Fibrogenic Activity in Hepatic Stellate Cells Through Autophagy.

Rosa S Kim, Daisuke Hasegawa, Nicolas Goossens, Takuma Tsuchida, Varinder Athwal, Xiaochen Sun, Christopher L Robinson, Dipankar Bhattacharya, Hsin-I Chou, David Y Zhang and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. 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
5.9field-weighted citation impact, top 4% 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, 101 citations in OpenAlex.

  1. Review
  2. FAM134B controls collagen I dynamics in hepatic stellate cell-driven fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025
    Review
  7. Article
  8. Article
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  11. Review
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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

14 authors at 4 institutions in 4 countries.

Rosa S KimDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Daisuke HasegawaDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Nicolas GoossensDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Takuma TsuchidaDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Varinder AthwalDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Xiaochen SunDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Christopher L RobinsonDepartment of Surgery, Weill Cornell Medical College, New York, US.
Dipankar BhattacharyaDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Hsin-I ChouDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
David Y ZhangDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Bryan C FuchsDivision of Surgical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, US.
Youngmin LeeDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Yujin HoshidaDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Scott L FriedmanDivision of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, US.
Icahn School of Medicine at Mount Sinai · USCornell University · USHarvard University · USMitsubishi Tanabe Pharma Corporation

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4M
MOUNT SINAI MEDICAL SCIENTIST TRAINING PROGRAMT32GM007280 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BARON, MARGARET H · 1985 to 2021
$22.8M
The Role of KLF6 in Hepatic FibrosisR01DK056621 · NIDDK · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI FRIEDMAN, SCOTT L. · 2000 to 2019
$6.2M
Studying the Progression and Regression of Beta Cell Dysfunction in Type 2 DiabetDP2DK098093 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2012 to 2017
$2.6M
Molecular Prognostic Indicators in Liver Cirrhosis and CancerR01DK099558 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOSHIDA, YUJIN · 2013 to 2016
$2.6M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
Autophagy during hepatic stellate cell activation in alcoholic liver injuryR01AA020709 · NIAAA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FRIEDMAN, SCOTT L. · 2011 to 2015
$1.8M
Medical Research Council G1001928NCI NIH HHS P30 CA196521NIAAA NIH HHS R01 AA020709NIDDK NIH HHS DP2 DK098093NIDDK NIH HHS R01 DK056621NIDDK NIH HHS R01 DK099558NIGMS NIH HHS T32 GM007280NIGMS NIH HHS T32 GM007739NIH HHS S10 OD018522
6 · The paper itself

Abstract

Autophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however the link between the two stimuli remains unclear. Here we have explored the role of X-box binding protein 1 (XBP1), one of three UPR effector pathways and sought to establish the interdependence between autophagy and the UPR during HSC activation. XBP1 induction accompanied both culture-based HSC activation and ER stress induced by tunicamycin. Ectopic overexpression of XBP1 induced collagen 1-alpha expression in HSCs, which was inhibited by knockdown of ATG7, a critical autophagy mediator. Genome-wide transcriptomic profiling indicated an upregulation of collagen synthesis pathways, but not of the transforming growth factor (TGF)-b pathway, a canonical fibrogenic driver, suggesting that XBP1 activates a specific subset of fibrogenesis pathways independent of TGF-β1. XBP1 target gene signatures were significantly induced in rodent liver fibrosis models (n = 3-5) and in human samples of non-alcoholic fatty liver disease (NAFLD) (n = 72-135). Thus, XBP1-mediated UPR contributes to fibrogenic HSC activation and is functionally linked to cellular autophagy.

Indexed as

AnimalsAutophagyAutophagy-Related Protein 7Cell LineCollagen Type IEndoplasmic Reticulum StressHEK293 CellsHepatic Stellate CellsHumansLiver CirrhosisMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseRNA InterferenceRNA, Small InterferingTunicamycinATG7 protein, humanAutophagy-Related Protein 7Collagen Type IRNA, Small InterferingTunicamycinX-Box Binding Protein 1XBP1 protein, human

Identifiers

PMID27996033
PMCPMC5172197
OpenAlexW2564335242

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.