ArticleCells2021
High Glucose Reduces the Paracellular Permeability of the Submandibular Gland Epithelium via the MiR-22-3p/Sp1/Claudin Pathway.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- The ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- [Research progress in diagnosis and treatment of non-tumorous salivary gland diseases].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- Article
- Identification of Key Efferocytosis-Related Genes and Mechanisms in Diabetic Retinopathy.Molecular biotechnology · 2025Article
- Loss of tricellular tight junction tricellulin leads to hyposalivation in Sjögren's syndrome.International journal of oral science · 2025Article
- Role of microRNAs in immunoregulatory functions of epithelial cells.BMC immunology · 2024Review
- MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts.Translational vision science & technology · 2023Article
- Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function.Nutrients · 2022Article
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Transcriptional Factors and Epigenetic Mechanisms in Obesity and Related Metabolic Comorbidities.Cells · 2022Article
- Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis.Bioengineered · 2022Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells; however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3'-untranslated region (3'-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.
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Registered trials
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