ArticleInflammatory bowel diseases2015
Involvement of heat shock protein a4/apg-2 in refractory inflammatory bowel disease.
Article in Inflammatory bowel diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Pilot Proteomic Analysis of Urinary Extracellular Vesicles Supports the "Toxic Urine Hypothesis" as a Vicious Cycle in Refractory IC/BPS Pathogenesis.International journal of molecular sciences · 2025Article
- Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma.International journal of molecular sciences · 2024Article
- Characterization of a New Hsp110 Inhibitor as a Potential Antifungal.Journal of fungi (Basel, Switzerland) · 2024Article
- Evaluation of the Genetic Diversity, Population Structure and Selection Signatures of Three Native Chinese Pig Populations.Animals : an open access journal from MDPI · 2023Article
- A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi.Nature communications · 2023Article
- Inhibition of DNAJC12 Inhibited Tumorigenesis of Rectal Cancer via Downregulating HSPA4 Expression.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Article
- Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis.Scientific reports · 2020Article
- Exosomes mediate intercellular transfer of non-autonomous tolerance to proteasome inhibitors in mixed-lineage leukemia.Cancer science · 2020Article
- Deficiency of Gankyrin in the small intestine is associated with augmented colitis accompanied by altered bacterial composition of intestinal microbiota.BMC gastroenterology · 2020Article
- Bioinformatics analysis of fibroblasts exposed to TGF‑β at the early proliferation phase of wound repair.Molecular medicine reports · 2017Article
- Gankyrin induces STAT3 activation in tumor microenvironment and sorafenib resistance in hepatocellular carcinoma.Cancer science · 2017Article
- Article
- The oncoprotein gankyrin promotes the development of colitis-associated cancer through activation of STAT3.Oncotarget · 2017Article
- Unfolding the Role of Large Heat Shock Proteins: New Insights and Therapeutic Implications.Frontiers in immunology · 2016Review
- Heat shock protein A4 controls cell migration and gastric ulcer healing.Digestive diseases and sciences · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExpression of heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, is induced by several forms of stress. The physiological and pathological functions of HSPA4 in the intestine remain to be elucidated.
methodsWe assessed HSPA4 expression and function by generating HSPA4-deficient mice and using 214 human intestinal mucosa samples from patients with inflammatory bowel disease (IBD).
resultsIn the colonic mucosa of patients with IBD, a significant correlation was observed between the expression of HSPA4 and antiapoptotic protein Bcl-2, a T-cell-derived cytokine IL-17 or stem cell markers, such as Sox2. In refractory ulcerative colitis, a condition associated with increased cancer risk, expression of HSPA4 and Bcl-2 was increased in inflammatory cells of colonic mucosae. HSPA4 was overexpressed both in cancer cells and immune cells of human colorectal cancers. Patients with high expression of HSPA4 or Bmi1 showed significantly lower response rates upon subsequent steroid therapy as compared with patients with low expression of each gene. HSPA4-deficient mice exhibit more apoptosis and less expression of IL-17/IL-23 in inflammatory cells and less number of Sox2 cells after administration of dextran sodium sulfate than control mice. Transduction of HspaA4 bone marrow into wild-type mice reduced the immune response.
conclusionsUpregulation of Bcl-2 and IL-17 by HSPA4 would control apoptosis of inflammatory cells and immune response in the gut, which might develop treatment resistance in IBD. HSPA4 and Bmi1 would be a useful biomarker for refractory clinical course and a promising approach for a therapeutic strategy in patients with IBD.
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