ArticleRespiratory research2019
Targeted regulation of fibroblast state by CRISPR-mediated CEBPA expression.
Article in Respiratory research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Laser-induced skin microenvironment remodeling via exosomal CEBPA-mediated crosstalk between keratinocyte and fibroblast.Journal of nanobiotechnology · 2026Article
- C/EBPγ interacts with C/EBPα and activates the β-catenin pathway in idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens.Nature communications · 2025Article
- Targeting the Epigenetic Regulator CBX5 Promotes Fibroblast Metabolic Reprogramming and Inhibits Lung Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Single-cell transcriptomics of vascularized human brain organoids decipher lineage-specific stress adaptation in fetal hypoxia-reoxygenation injury.Theranostics · 2025Article
- TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA.Nature communications · 2024Article
- Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The CEBPA-FGF21 regulatory network may participate in the T2DM-induced skeletal muscle atrophy by regulating the autophagy-lysosomal pathway.Acta diabetologica · 2023Article
- Quantitative Proteomic Analysis Reveals the Mechanisms of Sinapine Alleviate Macrophage Foaming.Molecules (Basel, Switzerland) · 2023Article
- C/EBPα promotes triacylglycerol synthesis via regulating PPARG promoter activity in goat mammary epithelial cells.Journal of animal science · 2023Article
- G9a promotes inflammation inAnnals of translational medicine · 2022Article
- Transcriptional analysis of lung fibroblasts identifies PIM1 signaling as a driver of aging-associated persistent fibrosis.JCI insight · 2022Article
- Perspectives on scaling production of adipose tissue for food applications.Biomaterials · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Fatty acid metabolism-related genes in bronchoalveolar lavage fluid unveil prognostic and immune infiltration in idiopathic pulmonary fibrosis.Frontiers in endocrinology · 2022Article
- Spontaneous Lung Fibrosis Resolution Reveals Novel Antifibrotic Regulators.American journal of respiratory cell and molecular biology · 2021Article
- Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis.Frontiers in physiology · 2021Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundFibroblasts regulate tissue homeostasis and the balance between tissue repair and fibrosis. CCAAT/enhancer-binding protein alpha (CEBPA) is a key transcription factor that regulates adipogenesis. CEBPA has been shown to be essential for lung maturation, and deficiency of CEBPA expression leads to abnormal lung architecture. However, its specific role in lung fibroblast regulation and fibrosis has not yet been elucidated.
methodsLung fibroblast CEBPA expression, pro-fibrotic and lipofibroblast gene expression were assessed by qRT-PCR. CEBPA gain and loss of function experiments were carried out to evaluate the role of CEBPA in human lung fibroblast activation with and without TGF-β1 treatment. Adipogenesis assay was used to measure the adiopogenic potential of lung fibroblasts. Finally, CRISPR activation system was used to enhance endogenous CEBPA expression.
resultsWe found that CEBPA gene expression is significantly decreased in IPF-derived fibroblasts compared to normal lung fibroblasts. CEBPA knockdown in normal human lung fibroblasts enhanced fibroblast pro-fibrotic activation and ECM production. CEBPA over-expression by transient transfection in IPF-derived fibroblasts significantly reduced pro-fibrotic gene expression, ECM deposition and αSMA expression and promoted the formation of lipid droplets measured by Oil Red O staining and increased lipofibroblast gene expression. Inhibition of the histone methyl transferase G9a enhanced CEBPA expression, and the anti-fibrotic effects of G9a inhibition were partially mediated by CEBPA expression. Finally, targeted CRISPR-mediated activation of CEBPA resulted in fibroblasts switching from fibrogenic to lipofibroblast states.
conclusionsCEBPA expression is reduced in human IPF fibroblasts and its deficiency reduces adipogenic potential and promotes fibrogenic activation. CEBPA expression can be rescued via an inhibitor of epigenetic repression or by targeted CRISPR activation, leading to reduced fibrogenic activation.
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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.