ArticleScientific reports2021
Metformin strengthens uroepithelial immunity against E. coli infection.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Metformin-Based Covalent Organic Frameworks With Excellent Biosafety and High Efficiency against Pathogenic Microorganisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cathelicidin in Urinary Tract Diseases: Diagnostic, Prognostic and Therapeutic Potential of an Evolutionary Conserved Antimicrobial Protein.Medicina (Kaunas, Lithuania) · 2024Review
- Current and emerging strategies to curb antibiotic-resistant urinary tract infections.Nature reviews. Urology · 2024Review
- Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets.Frontiers in physiology · 2024Review
- The Lysosomal Calcium Channel TRPML1 Maintains Mitochondrial Fitness in NK Cells through Interorganelle Cross-Talk.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- High Glucose Promotes Inflammation and Weakens Placental Defenses againstInternational journal of molecular sciences · 2023Article
- Repurposing HDAC inhibitors to enhance ribonuclease 4 and 7 expression and reduce urinary tract infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Emerging Roles of Growth Differentiation Factor 15 in Immunoregulation and Pathogenesis.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Recurrent urinary tract infection associated with SGLT-2 inhibitor in type 2 diabetes mellitus patient: A case report.Clinical case reports · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urinary tract infection frequently caused by E. coli is one of the most common bacterial infections. Increasing antibiotic resistance jeopardizes successful treatment and alternative treatment strategies are therefore mandatory. Metformin, an oral antidiabetic drug, has been shown to activate macrophages in the protection against certain infecting microorganisms. Since epithelial cells often form the first line of defense, we here investigated the effect on uroepithelial cells during E. coli infection. Metformin upregulated the human antimicrobial peptides cathelicidin LL-37 and RNase7 via modulation of the TRPA1 channel and AMPK pathway. Interestingly, metformin stimulation enriched both LL-37 and TRPA1 in lysosomes. In addition, metformin specifically increased nitric oxide and mitochondrial, but not cytosolic ROS. Moreover, metformin also triggered mRNA expression of the proinflammatory cytokines IL1B, CXCL8 and growth factor GDF15 in human uroepithelial cells. The GDF15 peptide stimulated macrophages increased LL-37 expression, with increased bacterial killing. In conclusion, metformin stimulation strengthened the innate immunity of uroepithelial cells inducing enhanced extracellular and intracellular bacterial killing suggesting a favorable role of metformin in the host defense.
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