ArticleGastroenterology2013
The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04114292 (A Phase I Open Label Study of the Efficacy and Safety of Tudca in Ulcerative Colitis), which is not on this map. Cited by 143 papers.
What it found
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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.
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.
A Phase I Open Label Study of the Efficacy and Safety of Tudca in Ulcerative Colitis
Who cites it
143 citing papers in PubMed, 231 citations in OpenAlex.
- Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1.Nutrients · 2019Trial
- Autophagy prevents ER stress-induced Tight Junction barrier disruption via claudin-2 homeostasis.bioRxiv : the preprint server for biology · 2026Article
- CHOP promotes the transition to chronic integrated stress response signaling with suppression of hepatocyte identity.bioRxiv : the preprint server for biology · 2026Article
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- Endoplasmic reticulum stress in skeletal muscle dysfunction of type 2 diabetes: mechanisms and therapeutic implications.Frontiers in endocrinology · 2026Review
- Bile Derivative T3K Ameliorates Colitis by Regulating the Intestinal Microbiota-Bile Acid Axis.Pharmaceutics · 2025Article
- MAPK signaling mediated intestinal inflammation induced by endoplasmic reticulum stress and NOD2.Molecular and cellular biochemistry · 2025Article
- CNPY2 drives DSS-induced colitis via the macrophage-ROS axis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- IRE1α and IRE1β Protect Intestinal Epithelium and Suppress Colorectal Tumorigenesis through Distinct Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Gut microbiota modulate intestinal inflammation by endoplasmic reticulum stress-autophagy-cell death signaling axis.Journal of animal science and biotechnology · 2025Review
- Tauroursodeoxycholic Acid (TUDCA) Reduces ER Stress and Lessens Disease Activity in Ulcerative Colitis.medRxiv : the preprint server for health sciences · 2025Article
- Article
- TUDCA modulates drug bioavailability to regulate resistance to acute ER stress inMolecular biology of the cell · 2025Article
- Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.European journal of immunology · 2025Article
- Effects of choline metabolite-trimethylamine N-oxide on immunometabolism in inflammatory bowel disease.Frontiers in immunology · 2025Review
- Endoplasmic reticulum stress and exosomes secretion in the pathogenesis of inflammatory bowel disease: a concise summary of research findings.Frontiers in pharmacology · 2025Review
- Unveiling the potential ofFrontiers in microbiology · 2025Review
- Bile Acids in Inflammatory Bowel Disease: From Pathophysiology to Treatment.Biomedicines · 2024Review
- Mucosal Single-Cell Profiling of Crohn's-Like Disease of the Pouch Reveals Unique Pathogenesis and Therapeutic Targets.Gastroenterology · 2024Article
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEndoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress-induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis.
methodsWe used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6α or the protein chaperone P58(IPK). We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58(IPK-/-), and Atf6α(-/-) mice with colitis; and in Il10(-/-) mice.
resultsP58(IPK-/-) and Atf6α(-/-) mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58(IPK-/-) mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6α(-/-) mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10(-/-) mice, and DSS-induced colitis in P58(IPK-/-) and Atf6α(-/-) mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells.
conclusionsThe unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases.
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Registered trials
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.