ArticleLung2016
HIF-1-Dependent TGM1 Expression is Associated with Maintenance of Airway Epithelial Junction Proteins.
Article in Lung, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
2 citing papers in PubMed, 6 citations in OpenAlex.
- Decoding the HIF-1-driven metabolic-inflammatory-immune axis in sepsis-associated lung injury: a comprehensive overview.Frontiers in immunology · 2025Review
- Transglutaminase 1: Emerging Functions beyond Skin.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHypoxia has been implicated in the pathogenesis of many inflammatory and fibrotic lung diseases. The effect of hypoxia on epithelial junction protein expression is yet to be fully elucidated but evidence suggests a protective role for the hypoxia-inducible transcription factor HIF-1 in stabilising occludin. Transglutaminase 1 (TGM1) has been shown to stabilise endothelial and keratinocyte cell junctions, and while its expression and function have been mostly studied in the skin, recent studies have reported its expression in the lung. We hypothesised that TGM1 is a hypoxia-induced regulator of pulmonary epithelial junction protein stability, and the aim of this study was to investigate the regulation of TGM1 expression by hypoxia.
methodsHypoxia-responsive genes were identified in human small airway epithelial cells (SAECs) by DNA microarray. TGM1 mRNA expression in SAECs was measured by quantitative real-time PCR. Protein expression of TGM1 and junction proteins was investigated by western blotting. Hypoxia-induced TGM1 was analysed by immunohistochemistry in vivo. The TGM1 gene promoter was investigated by luciferase assay.
resultsIn vitro exposure of SAECs to hypoxia induced a significant increase in TGM1 expression at both mRNA and protein levels. TGM1 was also significantly upregulated in hypoxic mouse lung epithelium. The hypoxia-responsive region was mapped to a HIF-1-responsive element. Inhibition of HIF-1 expression abolished hypoxia-induced promoter activation. Overexpression of TGM1 in lung epithelial cells or exposure of SAECs to hypoxia led to upregulated expression of junction proteins.
conclusionHerein we report that TGM1 is a HIF-1-regulated gene that is associated with the upregulation of airway epithelial junction proteins, supporting a protective role for HIF-1 in the lung. Interventions that augment the expression of TGM1 may provide useful therapeutic strategies for maintaining pulmonary epithelial integrity during lung injury.
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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 Socratic graph.