ArticleExperimental & molecular medicine2019
Blocking TBK1 alleviated radiation-induced pulmonary fibrosis and epithelial-mesenchymal transition through Akt-Erk inactivation.
Article in Experimental & molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Research trends and hot topics of radiation-induced pulmonary fibrosis: a bibliometric analysis and visualization study from 2015 to 2025.Journal of thoracic disease · 2026Article
- Natural compound 5,7,8‑trimethoxyflavone mitigates radiation‑induced lung injury by suppressing EMT and PI3K/Akt pathway.International journal of molecular medicine · 2026Article
- Aloe-emodin ameliorates chronic kidney disease fibrosis by inhibiting PI3K-mediated signaling pathway.European journal of histochemistry : EJH · 2025Article
- Serum Pharmacochemistry and Network Pharmacology Reveal Active Compounds and Mechanisms of the Huaxian Formula in Alleviating Radiation-Induced Pulmonary Fibrosis.Drug design, development and therapy · 2025Article
- Epithelial-mesenchymal transition in pulmonary fibrosis: molecular mechanisms and emerging therapeutic strategies.Frontiers in medicine · 2025Review
- The roles of TRPC6 in renal tubular disorders: a narrative review.Renal failure · 2024Review
- Review
- Mitochondria Energy Metabolism Depression as Novel Adjuvant to Sensitize Radiotherapy and Inhibit Radiation Induced-Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Emerging roles of TBK1 in cancer immunobiology.Trends in cancer · 2024Review
- Mechanism of Musashi2 affecting radiosensitivity of lung cancer by modulating DNA damage repair.MedComm · 2024Article
- SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.Cancer research · 2024Article
- 14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.Cell communication and signaling : CCS · 2024Review
- Emetine dihydrochloride alleviated radiation-induced lung injury through inhibiting EMT.Journal of cellular and molecular medicine · 2023Article
- The Promising Therapeutic Approaches for Radiation-Induced Pulmonary Fibrosis: Targeting Radiation-Induced Mesenchymal Transition of Alveolar Type II Epithelial Cells.International journal of molecular sciences · 2022Review
- Article
- Mouse mesenchymal stem cell-derived exosomal miR-466f-3p reverses EMT process through inhibiting AKT/GSK3β pathway via c-MET in radiation-induced lung injury.Journal of experimental & clinical cancer research : CR · 2022Article
- Lung Pneumonitis and Fibrosis in Cancer Therapy: A Review on Cellular and Molecular Mechanisms.Current drug targets · 2022Review
- Pharmacological Inhibition of STING/TBK1 Signaling Attenuates Myeloid Fibroblast Activation and Macrophage to Myofibroblast Transition in Renal Fibrosis.Frontiers in pharmacology · 2022Article
- Systems level insights into the impact of airborne exposure on SARS-CoV-2 pathogenesis and COVID-19 outcome - A multi-omics big data study.Gene reports · 2021Article
- TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation.American journal of physiology. Lung cellular and molecular physiology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
As a common serious complication of thoracic radiotherapy, radiation-induced pulmonary fibrosis (RIPF) severely limits radiation therapy approaches. Epithelial-mesenchymal transition (EMT) is a direct contributor to the fibroblast pool during fibrogenesis, and prevention of EMT is considered an effective strategy to inhibit tissue fibrosis. Our previous study revealed that TANK-binding kinase 1 (TBK1) regulates EMT in lung cancer cells. In the present study, we aimed to investigate the therapeutic potential of targeting TBK1 to prevent RIPF and EMT progression. We found radiation-induced EMT and pulmonary fibrosis in normal alveolar epithelial cells and lung tissues. TBK1 knockdown or inhibition significantly reversed EMT in vivo and in vitro and attenuated pulmonary fibrosis and collagen deposition. Moreover, we observed that TBK1 was elevated in a time- and dose-dependent manner by radiation. Meanwhile, radiation also induced time- and dose-dependent activation of AKT and ERK, each of whose inhibitors suppressed radiation-induced EMT. Intriguingly, silencing of TBK1 with shRNA also blocked the radiation-induced activation of AKT and ERK signaling. The ERK inhibitor did not obviously affect the expression of TBK1 or phosphorylated AKT, while AKT inhibition suppressed activation of ERK without changing the expression of TBK1. Finally, we found that a TBK1 inhibitor inhibited inflammatory cytokine expression in a RIPF model and Amlexanox protected normal cells and mice from ionizing radiation. In conclusion, our results indicate that the TBK1-AKT-ERK signaling pathway regulates radiation-induced EMT in normal alveolar epithelial cells, suggesting that TBK1 is a potential target for pulmonary fibrosis prevention during cancer radiotherapy.
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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.