ArticleFrontiers in immunology2021
Metformin-Inducible Small Heterodimer Partner Interacting Leucine Zipper Protein Ameliorates Intestinal Inflammation.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- Single-nucleus interrogation of primate small intestinal aging reveals NCoR1 decline as a conserved feature that is reversed by metformin.Nature aging · 2026Article
- Ulcerative colitis, pathophysiological mechanisms and drug repurposing: a new therapeutic dawn-narrative review.Inflammopharmacology · 2026Review
- Therapeutic impacts of oral anti-diabetic drugs on Inflammatory Bowel Disease (IBD), a comprehensive review of clinical and preclinical studies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Analysis of causal effects on metabolic syndrome and inflammatory bowel disease: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
- Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway.Arthritis research & therapy · 2024Article
- Small heterodimer partner interacting leucine zipper protein (SMILE) ameliorates autoimmune arthritis via AMPK signaling pathway and the regulation of B cell activation.Cell communication and signaling : CCS · 2023Article
- Emerging Role of SMILE in Liver Metabolism.International journal of molecular sciences · 2023Review
- Unveiling the key genes, environmental toxins, and drug exposures in modulating the severity of ulcerative colitis: a comprehensive analysis.Frontiers in immunology · 2023Review
- SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small heterodimer partner interacting leucine zipper protein (SMILE) is an orphan nuclear receptor and a member of the bZIP family of proteins. We investigated the mechanism by which SMILE suppressed the development of inflammatory bowel disease (IBD) using a DSS-induced colitis mouse model and peripheral blood mononuclear cells (PBMCs) from patients with ulcerative colitis (UC). Metformin, an antidiabetic drug and an inducer of AMPK, upregulated the level of SMILE in human intestinal epithelial cells and the number of SMILE-expressing cells in colon tissues from DSS-induced colitis mice compared to control mice. Overexpression of SMILE using a DNA vector reduced the severity of DSS-induced colitis and colitis-associated intestinal fibrosis compared to mock vector. Furthermore, SMILE transgenic mice showed ameliorated DSS-induced colitis compared with wild-type mice. The mRNA levels of SMILE and Foxp3 were downregulated and SMILE expression was positively correlated with Foxp3 in PBMCs from patients with UC and an inflamed mucosa. Metformin increased the levels of SMILE, AMPK, and Foxp3 but decreased the number of interleukin (IL)-17-producing T cells among PBMCs from patients with UC. These data suggest that SMILE exerts a therapeutic effect on IBD by modulating IL-17 production.
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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.