ArticlePloS one2012
Lipopolysaccharide induces lung fibroblast proliferation through Toll-like receptor 4 signaling and the phosphoinositide3-kinase-Akt pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
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- Variable steady inflammation and inflammatory responses in precision-cut lung slices from various IPF lung Regions.Respiratory research · 2025Article
- Fibroblast PI3K/AKT signaling and extracellular matrix homeostasis: mechanisms, targets, and delivery challenges.Frontiers in cell and developmental biology · 2025Review
- The mechanism of gut-lung axis in pulmonary fibrosis.Frontiers in cellular and infection microbiology · 2024Review
- Incomplete Knockdown of MyD88 Inhibits LPS-Induced Lung Injury and Lung Fibrosis in a Mouse Model.Inflammation · 2023Article
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- A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes.Molecules (Basel, Switzerland) · 2022Article
- PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases.Oxidative medicine and cellular longevity · 2022Review
- Baicalin relievesMolecular medicine reports · 2021Article
- Vimentin regulation of autophagy activation in lung fibroblasts in response to lipopolysaccharide exposure in vitro.Annals of translational medicine · 2021Article
- COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation.Mediators of inflammation · 2021Review
- Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations.Frontiers in immunology · 2021Review
- The Ameliorative Effects of Arctiin and Arctigenin on the Oxidative Injury of Lung Induced by Silica via TLR-4/NLRP3/TGF-Oxidative medicine and cellular longevity · 2021Article
- The Epithelial-Immune Crosstalk in Pulmonary Fibrosis.Frontiers in immunology · 2021Review
- Pathogenesis and treatment of idiopathic and rheumatoid arthritis-related interstitial pneumonia. The possible lesson from COVID-19 pneumonia.Expert review of clinical immunology · 2020Article
- PI3K-Akt-mTOR/PFKFB3 pathway mediated lung fibroblast aerobic glycolysis and collagen synthesis in lipopolysaccharide-induced pulmonary fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
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- Coelonin, an Anti-Inflammation Active Component ofInternational journal of molecular sciences · 2019Article
- Apoptosis Resistance in Fibroblasts Precedes Progressive Scarring in Pulmonary Fibrosis and Is Partially Mediated by Toll-Like Receptor 4 Activation.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary fibrosis is characterized by lung fibroblast proliferation and collagen secretion. In lipopolysaccharide (LPS)-induced acute lung injury (ALI), aberrant proliferation of lung fibroblasts is initiated in early disease stages, but the underlying mechanism remains unknown. In this study, we knocked down Toll-like receptor 4 (TLR4) expression in cultured mouse lung fibroblasts using TLR4-siRNA-lentivirus in order to investigate the effects of LPS challenge on lung fibroblast proliferation, phosphoinositide3-kinase (PI3K)-Akt pathway activation, and phosphatase and tensin homolog (PTEN) expression. Lung fibroblast proliferation, detected by BrdU assay, was unaffected by 1 mug/mL LPS challenge up to 24 hours, but at 72 hours, cell proliferation increased significantly. This proliferation was inhibited by siRNA-mediated TLR4 knockdown or treatment with the PI3K inhibitor, Ly294002. In addition, siRNA-mediated knockdown of TLR4 inhibited the LPS-induced up-regulation of TLR4, down-regulation of PTEN, and activation of the PI3K-Akt pathway (overexpression of phospho-Akt) at 72 hours, as detected by real-time PCR and Western blot analysis. Treatment with the PTEN inhibitor, bpV(phen), led to activation of the PI3K-Akt pathway. Neither the baseline expression nor LPS-induced down-regulation of PTEN in lung fibroblasts was influenced by PI3K activation state. PTEN inhibition was sufficient to exert the LPS effect on lung fibroblast proliferation, and PI3K-Akt pathway inhibition could reverse this process. Collectively, these results indicate that LPS can promote lung fibroblast proliferation via a TLR4 signaling mechanism that involves PTEN expression down-regulation and PI3K-Akt pathway activation. Moreover, PI3K-Akt pathway activation is a downstream effect of PTEN inhibition and plays a critical role in lung fibroblast proliferation. This mechanism could contribute to, and possibly accelerate, pulmonary fibrosis in the early stages of ALI/ARDS.
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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.