ArticleJCI insight2021
A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis.JCI insight · 2026Article
- BRG1 exacerbates myocardial fibrosis after myocardial infarction by interacting with ZEB1.Frontiers in pharmacology · 2026Article
- [Role ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Tumor suppressors RBL1 and PTEN are epigenetically silenced in IPF mesenchymal progenitor cells by a CD44/Brg1/PRMT5 regulatory complex.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Preclinical evidence in the assembly of mammalian SWI/SNF complexes: Epigenetic insights and clinical perspectives in human lung disease therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- A correctable immune niche for epithelial stem cell reprogramming and post-viral lung diseases.The Journal of clinical investigation · 2024Article
- Brg1/PRMT5 nuclear complex epigenetically regulates FOXO1 in IPF mesenchymal progenitor cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis.Journal of translational medicine · 2023Article
- Article
- SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2023Article
- Hypoxia enhances IPF mesenchymal progenitor cell fibrogenicity via the lactate/GPR81/HIF1α pathway.JCI insight · 2023Article
- Article
- SFPQ Promotes Lung Cancer MalignancyFrontiers in oncology · 2022Article
- Brahma-related gene-1 promotes tubular senescence and renal fibrosis through Wnt/β-catenin/autophagy axis.Clinical science (London, England : 1979) · 2021Article
- Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. We previously identified fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of patients with IPF who serve as drivers of progressive fibrosis. Recent single-cell RNA sequencing work revealed that IPF MPCs with the highest transcriptomic network entropy differ the most from control MPCs and that increased CD44 was a marker of these IPF MPCs. We hypothesize that IPF MPCs with high CD44 (CD44hi) expression will display enhanced fibrogenicity. We demonstrate that CD44-expressing MPCs are present at the periphery of the IPF fibroblastic focus, placing them in regions of active fibrogenesis. In a humanized mouse xenograft model, CD44hi IPF MPCs are more fibrogenic than CD44lo IPF MPCs, and knockdown of CD44 diminishes their fibrogenicity. CD44hi IPF MPCs display increased expression of pluripotency markers and enhanced self-renewal compared with CD44lo IPF MPCs, properties potentiated by IL-8. The mechanism involves the accumulation of CD44 within the nucleus, where it associates with the chromatin modulator protein Brahma-related gene 1 (Brg1) and the zinc finger E-box binding homeobox 1 (Zeb1) transcription factor. This CD44/Brg1/Zeb1 nuclear protein complex targets the Sox2 gene, promoting its upregulation and self-renewal. Our data implicate CD44 interaction with the epigenetic modulator protein Brg1 in conveying IPF MPCs with cell-autonomous fibrogenicity.
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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.