ArticleAmerican journal of respiratory and critical care medicine2018
Reversing Mechanoinductive DSP Expression by CRISPR/dCas9-mediated Epigenome Editing.
Article in American journal of respiratory and critical care medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- The Role of Monocytes in the Natural History of Idiopathic Pulmonary Fibrosis: A Systematic Literature Review.International journal of molecular sciences · 2025Pooled it
- SYISL promotes pulmonary epithelial-mesenchymal transition and fibrosis through DSP-Hippo/YAP pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues.Frontiers in cell and developmental biology · 2026Review
- Genomic and molecular evidence that the LncRNA DSP-AS1 modulates desmoplakin expression.Human genetics · 2025Article
- Matrix Stiffness-Mediated DNA Methylation in Endothelial Cells.Cellular and molecular bioengineering · 2025Article
- Ferroptosis in pulmonary fibrosis: pathogenesis and traditional Chinese medicine-driven therapeutic approaches.Frontiers in cell and developmental biology · 2025Review
- MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma.Medical review (2021) · 2024Article
- Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- A biomechanical view of epigenetic tumor regulation.Journal of biological physics · 2023Review
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Colocalization of Gene Expression and DNA Methylation with Genetic Risk Variants Supports Functional Roles ofAmerican journal of respiratory and critical care medicine · 2022Article
- Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.Journal of translational medicine · 2022Article
- Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?Advances in experimental medicine and biology · 2022Review
- Mechanical Cues Regulate Histone Modifications and Cell Behavior.Stem cells international · 2022Review
- Focusing on Mechanoregulation Axis in Fibrosis: Sensing, Transduction and Effecting.Frontiers in molecular biosciences · 2022Review
- DNA Methylome Alterations Are Associated with Airway Macrophage Differentiation and Phenotype during Lung Fibrosis.American journal of respiratory and critical care medicine · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleDSP (desmoplakin), the most abundant component of desmosomes, which maintain the mechanical integrity of epithelium, is a genome-wide association study-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). Subjects with IPF express a significantly higher level of DSP than control subjects.
objectivesDetermine potential mechanisms by which DSP is regulated in lung fibrosis.
methodsMatrigel-coated soft and stiff polyacrylamide gels were made to simulate the stiffness of normal and fibrotic lungs. Quantitative chromatin immunoprecipitation and electrophoretic mobility shift assay were used to evaluate transcription factor binding to the DSP promoter. Targeted DNA methylation was achieved by CRISPR (clustered regularly interspaced short palindromic repeats)/dCas9 (deactivated CRISPR-associated protein-9 nuclease)-mediated Dnmt3A (DNA methyltransferase 3A) expression under the guidance of sequence-specific single guide RNAs. MEASUREMENTS AND MAIN
resultsStiff matrix promotes DSP gene expression in both human and rodent lung epithelial cells as compared with soft matrix. A conserved region in the proximal DSP promoter is hypermethylated under soft matrix conditions and becomes hypomethylated/demethylated under stiff matrix conditions. Demethylation of this conserved DSP promoter region is associated with transactivation of transcription factor EGR1 (early growth response protein 1), resulting in EGR1-dependent DSP overexpression. Targeted DNA methylation by CRISPR/dCas9/Dnmt3A-mediated epigenome editing blocks EGR1 binding to the DSP promoter and inhibits stiff matrix-induced DSP overexpression.
conclusionsDSP is a matrix stiffness-regulated mechanosensitive gene. CRISPR/dCas9-Dnmt3A-mediated epigenome editing reverses DSP overexpression by reestablishment of the epigenetic control of DSP under the mechanically homeostatic environment. It provides a useful tool for investigations of the functional role of DSP in the pathogenesis of lung fibrosis.
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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.