ArticleJournal of cell science2018
RNAi screening identifies a mechanosensitive ROCK-JAK2-STAT3 network central to myofibroblast activation.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Identifying regulators of aged fibroblast activation in 3D tissue models.Scientific reports · 2025Article
- Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis.Nature communications · 2025Article
- APEX1-STAT3 signaling mediates the force-coordinated endothelial regeneration.Cellular and molecular life sciences : CMLS · 2025Article
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote IL6-dependent fibroblast activation.Cell biomaterials · 2025Article
- Trpv4-mediated mechanotransduction regulates the differentiation of valvular interstitial cells to myofibroblasts: implications for aortic valve stenosis.American journal of physiology. Cell physiology · 2025Article
- Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants.Biomaterials · 2025Article
- Genome-wide CRISPR/Cas9 screening identifies key profibrotic regulators of TGF-β1-induced epithelial-mesenchymal transformation and pulmonary fibrosis.Frontiers in molecular biosciences · 2025Article
- Imaging methods to monitor and quantify cell differentiation.Frontiers in cell and developmental biology · 2025Review
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies.Clinical reviews in allergy & immunology · 2023Review
- The Role of Myofibroblasts in Physiological and Pathological Tissue Repair.Cold Spring Harbor perspectives in biology · 2023Review
- Pim-1 kinase is a positive feedback regulator of the senescent lung fibroblast inflammatory secretome.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Vascular smooth muscle cells in intimal hyperplasia, an update.Frontiers in physiology · 2022Review
- Exogenous extracellular matrix proteins decrease cardiac fibroblast activation in stiffening microenvironment through CAPG.Journal of molecular and cellular cardiology · 2021Article
- The Role of Rho GTPases During Fibroblast Spreading, Migration, and Myofibroblast Differentiation in 3D Synthetic Fibrous Matrices.Cellular and molecular bioengineering · 2021Article
- Review
- New promising drugs for the treatment of systemic sclerosis: pathogenic considerations, enhanced classifications, and personalized medicine.Expert opinion on investigational drugs · 2021Review
- ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation.The Journal of cell biology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Myofibroblasts play key roles in wound healing and pathological fibrosis. Here, we used an RNAi screen to characterize myofibroblast regulatory genes, using a high-content imaging approach to quantify α-smooth muscle actin stress fibers in cultured human fibroblasts. Screen hits were validated on physiological compliance hydrogels, and selected hits tested in primary fibroblasts from patients with idiopathic pulmonary fibrosis. Our RNAi screen led to the identification of STAT3 as an essential mediator of myofibroblast activation and function. Strikingly, we found that STAT3 phosphorylation, while responsive to exogenous ligands on both soft and stiff matrices, is innately active on a stiff matrix in a ligand/receptor-independent, but ROCK- and JAK2-dependent fashion. These results demonstrate how a cytokine-inducible signal can become persistently activated by pathological matrix stiffening. Consistent with a pivotal role for this pathway in driving persistent fibrosis, a STAT3 inhibitor attenuated murine pulmonary fibrosis when administered in a therapeutic fashion after bleomycin injury. Our results identify novel genes essential for the myofibroblast phenotype, and point to STAT3 as an important target in pulmonary fibrosis and other fibrotic diseases.
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Registered trials
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.