ArticleThe Journal of clinical investigation2018
Expression of mutant Sftpc in murine alveolar epithelia drives spontaneous lung fibrosis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.
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Who cites it
162 citing papers in PubMed, 1 synthesis or guideline pooled it, 254 citations in OpenAlex.
- The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis.Scientific reports · 2021Pooled it
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Peptide additives reprogram the lipid nanoparticle corona and enhance gene delivery in a serum-free environment for lung epithelium.bioRxiv : the preprint server for biology · 2026Article
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- Murine models of pulmonary fibrosis: mechanisms, limitations and translational insights.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- 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
- Interstitial lung disease and the STING pathway.The Journal of clinical investigation · 2026Review
- Review
- Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Biomarker exploration for immunotherapy plus chemotherapy following resistance to third-generation EGFR-TKIs in lung adenocarcinoma.BMC cancer · 2026Article
- Advancing dual gene therapy for SFTPC deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Lung-tropic dual AAV-SP-C and microRNA gene therapy attenuates lung injury in mutant Sftpc mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Syndecan-1 Promotes Alveolar Type 2 Epithelial Cell Senescence during Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Regulatory T cells protect against aberrant remodeling in a mouse model of pulmonary fibrosis.Mucosal immunology · 2026Article
- TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Cells · 2026Review
- Divergent pathways of surfactant protein C maturation for disease-associated isoforms.The Journal of biological chemistry · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
102 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Epithelial cell dysfunction is postulated as an important component in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mutations in the surfactant protein C (SP-C) gene (SFTPC), an alveolar type II (AT2) cell-restricted protein, have been found in sporadic and familial IPF. To causally link these events, we developed a knockin mouse model capable of regulated expression of an IPF-associated isoleucine-to-threonine substitution at codon 73 (I73T) in Sftpc (SP-CI73T). Tamoxifen-treated SP-CI73T cohorts developed rapid increases in SftpcI73T mRNA and misprocessed proSP-CI73T protein accompanied by increased early mortality (days 7-14). This acute phase was marked by diffuse parenchymal lung injury, tissue infiltration by monocytes, polycellular alveolitis, and elevations in bronchoalveolar lavage and AT2 mRNA content of select inflammatory cytokines. Resolution of alveolitis (2-4 weeks), commensurate with a rise in TGF-β1, was followed by aberrant remodeling marked by collagen deposition, AT2 cell hyperplasia, α-smooth muscle actin-positive (α-SMA-positive) cells, and restrictive lung physiology. The translational relevance of the model was supported by detection of multiple IPF biomarkers previously reported in human cohorts. These data provide proof of principle that mutant SP-C expression in vivo causes spontaneous lung fibrosis, strengthening the role of AT2 cell dysfunction as a key upstream driver of IPF pathogenesis.
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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.