ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Sustained YAP/TAZ activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling.JCI insight · 2026Article
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Review
- Chronic mechanical irritation as a potential contributor to nasal fibroma formation in a captive Javanese cownose ray (Frontiers in veterinary science · 2026Article
- Targeting the Epigenetic Regulator CBX5 Promotes Fibroblast Metabolic Reprogramming and Inhibits Lung Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- The mechanobiology of fibroblast activation in disease.APL bioengineering · 2025Review
- p21-Activated Kinase 1 (Pak1) as an Element in Functional and Dysfunctional Interplay Among the Myocardium, Adipose Tissue, and Pancreatic Beta Cells.Comprehensive Physiology · 2025Review
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Review
- Article
- Non-canonical IKB kinases regulate YAP/TAZ and pathological vascular remodeling behaviors in pulmonary artery smooth muscle cells.Physiological reports · 2024Article
- Divergent roles of the Hippo pathway in the pathogenesis of idiopathic pulmonary fibrosis: tissue homeostasis and fibrosis.Inflammation and regeneration · 2023Review
- Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury.JCI insight · 2023Article
- Dopamine Receptor D1 Is Exempt from Transforming Growth FactorThe Journal of pharmacology and experimental therapeutics · 2023Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Mechanosensation to inflammation: Roles for YAP/TAZ in innate immune cells.Science signaling · 2023Review
- FOXC2-AS1/FOXC2 axis mediates matrix stiffness-induced trans-differentiation of hepatic stellate cells into fibrosis-promoting myofibroblasts.International journal of biological sciences · 2023Article
- Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals.Inflammopharmacology · 2022Review
- Review
- Regulator of G protein signaling 2 inhibits GαThe Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) results in scarring of the lungs by excessive extracellular matrix (ECM) production. Resident fibroblasts are the major cell type involved in ECM deposition. The biochemical pathways that facilitate pathological fibroblast activation leading to aberrant ECM deposition are not fully understood. Tank binding protein kinase-1 (TBK1) is a kinase that regulates multiple signaling pathways and was recently identified as a candidate regulator of fibroblast activation in a large-scale small-interfering RNA (siRNA) screen. To determine the effect of TBK1 on fibroblast activation, TBK1 was inhibited pharmacologically (MRT-68601) and genetically (siRNA) in normal and IPF human lung fibroblasts. Reducing the activity or expression of TBK1 led to reduction in α-smooth muscle actin stress fiber levels by 40-60% and deposition of ECM components collagen I and fibronectin by 50% in TGF-β-stimulated normal and IPF fibroblasts. YAP and TAZ are homologous mechanoregulatory profibrotic transcription cofactors known to regulate fibroblast activation. TBK1 knockdown or inhibition decreased the total and nuclear protein levels of YAP/TAZ. Additionally, low cell-cell contact and increased ECM substrate stiffness augmented the phosphorylation and activation of TBK1, consistent with cues that regulate YAP/TAZ. The action of TBK1 toward YAP/TAZ activation was independent of LATS1/2 and canonical downstream TBK1 signaling mediator IRF3 but dependent on proteasomal machinery of the cell. This study identifies TBK1 as a fibrogenic activator of human pulmonary fibroblasts, suggesting TBK1 may be a novel therapeutic target in pulmonary fibrosis.
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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 Socratic graph.