ArticlePLoS pathogens2015
Role of Hypoxia Inducible Factor-1α (HIF-1α) in Innate Defense against Uropathogenic Escherichia coli Infection.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed.
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Article
- Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression:International journal of molecular sciences · 2024Article
- Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model.Scientific reports · 2024Article
- Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.Critical care (London, England) · 2024Review
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- A Bird's-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It?Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Chemical profiling of Sanjin tablets and exploration of their effective substances and mechanism in the treatment of urinary tract infections.Frontiers in chemistry · 2023Article
- The effect of HIF on metabolism and immunity.Nature reviews. Nephrology · 2022Review
- Uropathogenic Escherichia coli subverts mitochondrial metabolism to enable intracellular bacterial pathogenesis in urinary tract infection.Nature microbiology · 2022Article
- Immunomodulation therapy offers new molecular strategies to treat UTI.Nature reviews. Urology · 2022Review
- Syncytin-1 nonfusogenic activities modulate inflammation and contribute to preeclampsia pathogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Stabilization but No Functional Influence of HIF-1α Expression in the Intestinal Epithelium during Salmonella Typhimurium Infection.Infection and immunity · 2022Article
- Article
- ROS-responsive nanoparticle-mediated delivery of CYP2J2 gene for therapeutic angiogenesis in severe hindlimb ischemia.Materials today. Bio · 2022Article
- HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Molecular determinants of disease severity in urinary tract infection.Nature reviews. Urology · 2021Review
- The microbiome and host mucosal interactions in urinary tract diseases.Mucosal immunology · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Uropathogenic E. coli (UPEC) is the primary cause of urinary tract infections (UTI) affecting approximately 150 million people worldwide. Here, we revealed the importance of transcriptional regulator hypoxia-inducible factor-1 α subunit (HIF-1α) in innate defense against UPEC-mediated UTI. The effects of AKB-4924, a HIF-1α stabilizing agent, were studied using human uroepithelial cells (5637) and a murine UTI model. UPEC adherence and invasion were significantly reduced in 5637 cells when HIF-1α protein was allowed to accumulate. Uroepithelial cells treated with AKB-4924 also experienced reduced cell death and exfoliation upon UPEC challenge. In vivo, fewer UPEC were recovered from the urine, bladders and kidneys of mice treated transurethrally with AKB-4924, whereas increased bacteria were recovered from bladders of mice with a HIF-1α deletion. Bladders and kidneys of AKB-4924 treated mice developed less inflammation as evidenced by decreased pro-inflammatory cytokine release and neutrophil activity. AKB-4924 impairs infection in uroepithelial cells and bladders, and could be correlated with enhanced production of nitric oxide and antimicrobial peptides cathelicidin and β-defensin-2. We conclude that HIF-1α transcriptional regulation plays a key role in defense of the urinary tract against UPEC infection, and that pharmacological HIF-1α boosting could be explored further as an adjunctive therapy strategy for serious or recurrent UTI.
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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.