ReviewClinical reviews in allergy & immunology2017
Significance of Interleukin-6/STAT Pathway for the Gene Expression of REG Iα, a New Autoantigen in Sjögren's Syndrome Patients, in Salivary Duct Epithelial Cells.
Review in Clinical reviews in allergy & immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Evaluating the efficacy of stem cells in treating severe dry eye disease.World journal of stem cells · 2025Review
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- CRISPR-Cas9 editing ofFrontiers in genome editing · 2025Article
- Controversial Roles of Regenerating Family Proteins in Tissue Repair and Tumor Development.Biomedicines · 2024Review
- The Reg protein family: potential new targets for the treatment of inflammatory bowel disease and colorectal cancer.Frontiers in gastroenterology (Lausanne, Switzerland) · 2024Review
- Current Advances in Regenerative Strategies for Dry Eye Diseases: A Comprehensive Review.Bioengineering (Basel, Switzerland) · 2023Review
- Upregulation ofInternational journal of molecular sciences · 2022Article
- Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract.International journal of molecular sciences · 2021Review
- Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular CaProceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Article
- The Relevance of Regenerating Gene 1a Polymorphisms to Radiation Sensitivity and Survival of Nasopharyngeal Carcinoma Receiving Radiotherapy in a Southern Chinese Population.Pharmacogenomics and personalized medicine · 2021Article
- The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues.Mediators of inflammation · 2019Article
- Autoimmunity in 2017.Clinical reviews in allergy & immunology · 2018Review
- The Clinical Significance of GP73 in Immunologically Mediated Chronic Liver Diseases: Experimental Data and Literature Review.Clinical reviews in allergy & immunology · 2018Review
- Remission of Sjogren's Syndrome after Roux-en-Y Gastric Bypass for Morbid Obesity.Obesity surgery · 2018Article
- Role of regenerating gene IA expression on local invasion and survival in nasopharyngeal carcinoma.Biological research · 2017Article
- Autoimmunity in 2016.Clinical reviews in allergy & immunology · 2017Review
- Mitogen-activated protein kinase p38 target regenerating islet-derived 3γ expression is upregulated in cardiac inflammatory response in the rat heart.Physiological reports · 2016Article
- Mesenchymal Stromal Cell-Based Therapy for Dry Eye: Current Status and Future Perspectives.Cell transplantationReview
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regenerating gene, Reg, was originally isolated from a rat regenerating islet complementary DNA (cDNA) library, and its human homologue was named REG Iα. Recently, we reported that REG Iα messenger RNA (mRNA), as well as its product, was overexpressed in ductal epithelial cells in the salivary glands of Sjögren's syndrome patients. Furthermore, autoantibodies against REG Iα were found in the sera of Sjögren's syndrome patients, and the patients who were positive for the anti-REG Iα antibody showed significantly lower saliva secretion than antibody-negative patients. We found the mechanism of REG Iα induction in salivary ductal epithelial cells. Reporter plasmid containing REG Iα promoter (-1190/+26) upstream of a luciferase gene was introduced into human NS-SV-DC and rat A5 salivary ductal cells. The cells were treated with several cytokines (interleukin (IL)-6, IL-8, etc.), upregulated in Sjögren's syndrome salivary ducts, and the transcriptional activity was measured. IL-6 stimulation significantly enhanced the REG Iα promoter activity in both cells. Deletion analysis revealed that the -141∼-117 region of the REG Iα gene was responsible for the promoter activation by IL-6, which contains a consensus sequence for signal transducer and activator of transcription (STAT) binding. The introduction of small interfering RNA for human STAT3 abolished IL-6-induced REG Iα transcription. These results indicated that IL-6 stimulation induced REG Iα transcription through STAT3 activation and binding to the REG Iα promoter in salivary ductal cells. This dependence of REG Iα induction upon IL-6/STAT in salivary duct epithelial cells may play an important role in the pathogenesis/progression of Sjögren's syndrome.
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