ArticleeLife2022
Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Salvianolic Acid B Inhibited LH2 Expression to Reduce Collagen Synthesis in Pulmonary Fibrosis.Journal of cellular and molecular medicine · 2026Article
- Mapping cellular and ECM heterogeneity in pulmonary fibrosis - insights from recent spatiomics studies.Cell biomaterials · 2026Article
- MUUMI: an R package for statistical and network-based meta-analysis for multi-omics data integration.BMC bioinformatics · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Attenuating amiodarone-induced lung toxicity by the vitamin D receptor activator paricalcitol in rats: targeting TLR4/NF-κB/HIF-1α and TGF-β/Smad signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Stem cell-derived extracellular vesicles for high-altitude skin injuries: pathological mechanisms, advanced Nano-delivery, and translational perspectives.Frontiers in bioengineering and biotechnology · 2026Review
- Unraveling the role of HIF-1 in peripheral blood mononuclear cells from older patients with Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Curated and harmonised transcriptomics datasets of interstitial lung diseases.Data in brief · 2025Article
- Improved Translational Relevance of In Vitro Fibrosis Models by Integrating IOX2-Mediated Hypoxia-Mimicking Pathways.Biomedicines · 2025Article
- An in vitro model of the epithelial airway reveals a key function for EHF in lung homeostasis and disease.Disease models & mechanisms · 2025Article
- Female Fibroblast Activation Is Estrogen-Mediated in Sex-Specific 3D-Bioprinted Pulmonary Artery Adventitia Models.ACS biomaterials science & engineering · 2025Article
- A Boolean network model of hypoxia, mechanosensing and TGF-β signaling captures the role of phenotypic plasticity and mutations in tumor metastasis.PLoS computational biology · 2025Article
- Revealing a Novel Methylated Integrin Alpha-8 Related to Extracellular Matrix and Anoikis Resistance Using Proteomic Analysis in the Immune Microenvironment of Lung Adenocarcinoma.Molecular biotechnology · 2025Article
- Copper-enriched automotive brake wear particles perturb human alveolar cellular homeostasis.Particle and fibre toxicology · 2025Article
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion.Bulletin of mathematical biology · 2025Article
- Targeting hypoxia-inducible factor 1α in chronic graft-versus-host disease to enhance graft-versus-leukemia responses: implications for nanotherapeutics.Frontiers in immunology · 2025Review
- Hox gene activity directs physical forces to differentially shape chick small and large intestinal epithelia.Developmental cell · 2024Article
Corrections and comments
- Commented on by
Authors and funding
29 authors at 7 institutions in 6 countries.
Funding
Abstract
Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we provide evidence that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of the oxygen status (pseudohypoxia). Whilst TGFβ increased the rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting pyridinoline cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knockdown of Factor Inhibiting HIF (FIH), which modulates HIF activity, or oxidative stress caused pseudohypoxic HIF activation in the normal fibroblasts. By contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF-mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of human lung fibrosis mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
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.