ArticleJCI insight2019
An SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- Impact of Cardiovascular Diseases on COVID-19: A Systematic Review.Medical science monitor : international medical journal of experimental and clinical research · 2021Pooled it
- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Murine models of pulmonary fibrosis: mechanisms, limitations and translational insights.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Transitional cell states at the crossroads of development, disease, and repair-regeneration.Physiological reviews · 2026Review
- The Genetic Landscape of Fibrotic Interstitial Lung Diseases: Clinical Implications and Diagnostic Challenges in Familial Pulmonary Fibrosis.Journal of clinical medicine · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Biomarker exploration for immunotherapy plus chemotherapy following resistance to third-generation EGFR-TKIs in lung adenocarcinoma.BMC cancer · 2026Article
- Regulatory T cells protect against aberrant remodeling in a mouse model of pulmonary fibrosis.Mucosal immunology · 2026Article
- Divergent pathways of surfactant protein C maturation for disease-associated isoforms.The Journal of biological chemistry · 2026Article
- The Impact of Genetics on Pediatric Interstitial Lung Diseases: A Narrative Literature Review and Clinical Implications.Biomedicines · 2026Review
- Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice.NPJ Regenerative medicine · 2026Article
- Targeting the epithelium in pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- HECTD1-mediated SFTPB overexpression in fibrotic lung induced by silica.Biochemistry and biophysics reports · 2025Article
- Matrix Metalloproteinase-9 (MMP-9) as a Therapeutic Target: Insights into Molecular Pathways and Clinical Applications.Pharmaceutics · 2025Review
- Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms.bioRxiv : the preprint server for biology · 2025Article
- Aberrant intermediate alveolar epithelial cells promote pathogenic activation of lung fibroblasts in preclinical fibrosis models.Nature communications · 2025Article
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Alveolar type 2 (AT2) cell endoplasmic reticulum (ER) stress is a prominent feature in adult and pediatric interstitial lung disease (ILD and ChILD), but in vivo models linking AT2 cell ER stress to ILD have been elusive. Based on a clinical ChILD case, we identified a critical cysteine residue in the surfactant protein C gene (SFTPC) BRICHOS domain whose mutation induced ER stress in vitro. To model this in vivo, we generated a knockin mouse model expressing a cysteine-to-glycine substitution at codon 121 (C121G) in the Sftpc gene. SftpcC121G expression during fetal development resulted in a toxic gain-of-function causing fatal postnatal respiratory failure from disrupted lung morphogenesis. Induced SftpcC121G expression in adult mice resulted in an ER-retained pro-protein causing AT2 cell ER stress. SftpcC121G AT2 cells were a source of cytokines expressed in concert with development of polycellular alveolitis. These cytokines were subsequently found in a high-dimensional proteomic screen of bronchoalveolar lavage fluid from ChILD patients with the same class of SFTPC mutations. Following alveolitis resolution, SftpcC121G mice developed spontaneous pulmonary fibrosis and restrictive lung impairment. This model provides proof of concept linking AT2 cell ER stress to fibrotic lung disease coupled with translationally relevant biomarkers.
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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.