ArticleAmerican journal of physiology. Lung cellular and molecular physiology2022
IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- RelA Signaling inInternational journal of molecular sciences · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Transcriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice.Nature communications · 2026Article
- Postnatal Abrogation of VEGFR2 Blocks Terminal Cap2 Differentiation by Preventing the Developmental Progression from a Capillary Intermediate Cell State.bioRxiv : the preprint server for biology · 2025Article
- Stress, plasticity, and fibrosis: unfolding the role of the IRE1α/RIDD/Fgfr2 axis.The Journal of clinical investigation · 2025Article
- Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice.The Journal of clinical investigation · 2025Article
- A molecular circuit regulates fate plasticity in emerging and adult AT2 cells.Nature communications · 2025Article
- Evidence that metformin promotes fibrosis resolutionActa pharmaceutica Sinica. B · 2025Article
- Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
- An orally bioavailable BRD4 inhibitor disrupts expansion of a pathogenic epithelial-mesenchymal niche in bleomycin-induced fibrosis.Respiratory research · 2025Article
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- Mechanisms on How Matricellular Microenvironments Sustain Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- Alveolar epithelial type 2 cells in acute lung injury and acute respiratory distress syndrome: spatiotemporal fate and regulation.Burns & trauma · 2025Review
- Dysregulated alveolar epithelial cell progenitor function and identity in Hermansky-Pudlak syndrome.JCI insight · 2024Article
- Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration.Nature communications · 2024Article
- Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Cell-cell interactions and communication dynamics in lung fibrosis.Chinese medical journal pulmonary and critical care medicine · 2024Review
- BCL-2 Modulates IRE1α Activation to Attenuate Endoplasmic Reticulum Stress and Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- IRE1 RNase controls CD95-mediated cell death.EMBO reports · 2024Article
- Understanding the impact of ER stress on lung physiology.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
After lung injury, damage-associated transient progenitors (DATPs) emerge, representing a transitional state between injured epithelial cells and newly regenerated alveoli. DATPs express profibrotic genes, suggesting that they might promote idiopathic pulmonary fibrosis (IPF). However, the molecular pathways that induce and/or maintain DATPs are incompletely understood. Here we show that the bifunctional kinase/RNase-IRE1α-a central mediator of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress is a critical promoter of DATP abundance and function. Administration of a nanomolar-potent, monoselective kinase inhibitor of IRE1α (KIRA8)-or conditional epithelial IRE1α gene knockout-both reduce DATP cell number and fibrosis in the bleomycin model, indicating that IRE1α cell-autonomously promotes transition into the DATP state. IRE1α enhances the profibrotic phenotype of DATPs since KIRA8 decreases expression of integrin αvβ6, a key activator of transforming growth factor β (TGF-β) in pulmonary fibrosis, corresponding to decreased TGF-β-induced gene expression in the epithelium and decreased collagen accumulation around DATPs. Furthermore, IRE1α regulates DNA damage response (DDR) signaling, previously shown to promote the DATP phenotype, as IRE1α loss-of-function decreases H2AX phosphorylation,
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