ArticleJCI insight2018
Localized hypoxia links ER stress to lung fibrosis through induction of C/EBP homologous protein.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 83 citations in OpenAlex.
- Single‑cell and spatial transcriptomics in chronic lung disease: cellular heterogeneity and molecular mechanisms in IPF and COPD.Respiratory research · 2026Review
- C/EBPγ interacts with C/EBPα and activates the β-catenin pathway in idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting the epithelium in pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Modulation of an aberrant basal cell program in human alveolar epithelial spheroids and lung slices.Respiratory research · 2025Article
- Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice.The Journal of clinical investigation · 2025Article
- The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.International journal of molecular sciences · 2025Review
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- Decoding the complexity: mechanistic insights into comorbidities in idiopathic pulmonary fibrosis.The European respiratory journal · 2025Review
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- Vascular volume changes in radiological patterns of usual interstitial pneumonia in patients with type 2 diabetes.Diabetology & metabolic syndrome · 2024Article
- Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis.Respiratory research · 2024Article
- Tribbles pseudokinase 3 promoted renal fibrosis by regulating the expression of DNA damage-inducible transcript 3 in diabetic nephropathy.Biomolecules & biomedicine · 2024Article
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- Effects of Natural Products through Inhibiting Endoplasmic Reticulum Stress on Attenuation of Idiopathic Pulmonary Fibrosis.Drug design, development and therapy · 2024Review
- Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway.Journal of orthopaedic surgery and research · 2023Article
- Integrated analysis reveals the protective mechanism and therapeutic potential of hyperbaric oxygen against pulmonary fibrosis.Genes & diseases · 2023Article
- Integrating the Integrated Stress Response.American journal of respiratory cell and molecular biology · 2023Article
- Epithelial Endoplasmic Reticulum Stress Enhances the Risk of Muc5b-associated Lung Fibrosis.American journal of respiratory cell and molecular biology · 2023Article
- Biology of Stress Responses in Aging.Aging biology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
ER stress in type II alveolar epithelial cells (AECs) is common in idiopathic pulmonary fibrosis (IPF), but the contribution of ER stress to lung fibrosis is poorly understood. We found that mice deficient in C/EBP homologous protein (CHOP), an ER stress-regulated transcription factor, were protected from lung fibrosis and AEC apoptosis in 3 separate models where substantial ER stress was identified. In mice treated with repetitive intratracheal bleomycin, we identified localized hypoxia in type II AECs as a potential mechanism explaining ER stress. To test the role of hypoxia in lung fibrosis, we treated mice with bleomycin, followed by exposure to 14% O2, which exacerbated ER stress and lung fibrosis. Under these experimental conditions, CHOP-/- mice, but not mice with epithelial HIF (HIF1/HIF2) deletion, were protected from AEC apoptosis and fibrosis. In vitro studies revealed that CHOP regulates hypoxia-induced apoptosis in AECs via the inositol-requiring enzyme 1α (IRE1α) and the PKR-like ER kinase (PERK) pathways. In human IPF lungs, CHOP and hypoxia markers were both upregulated in type II AECs, supporting a conclusion that localized hypoxia results in ER stress-induced CHOP expression, thereby augmenting type II AEC apoptosis and potentiating lung fibrosis.
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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.