ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
p70 ribosomal S6 kinase regulates subpleural fibrosis following transforming growth factor-α expression in the lung.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacological repurposing of cilostazol to attenuate the progression of pulmonary fibrosis: efficacy validation via integrated network pharmacology and in vivo experimentation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.Cancer research communications · 2024Article
- SEMA3B inhibits TGFβ-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF.American journal of physiology. Cell physiology · 2024Article
- Role and targeting of the AGC kinase family in pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2024Review
- The mTORC2/SGK1/NDRG1 Signaling Axis Is Critical for the Mesomesenchymal Transition of Pleural Mesothelial Cells and the Progression of Pleural Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Nε-Carboxymethyl-Lysine Modification of Extracellular Matrix Proteins Augments Fibroblast Activation.International journal of molecular sciences · 2023Article
- Downregulation of histone deacetylase 8 (HDAC8) alleviated the progression of oral submucous fibrosis.Journal of dental sciences · 2023Article
- Article
- A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis.JCI insight · 2022Article
- Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis.JCI insight · 2021Article
- Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis.EMBO molecular medicine · 2020Article
- MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway.EBioMedicine · 2020Article
- Dysregulation of Mesenchymal Cell Survival Pathways in Severe Fibrotic Lung Disease: The Effect of Nintedanib Therapy.Frontiers in pharmacology · 2019Article
- New therapeutics based on emerging concepts in pulmonary fibrosis.Expert opinion on therapeutic targets · 2019Review
- Upregulation of long noncoding RNA AP003419.16 predicts high risk of aging‑associated idiopathic pulmonary fibrosis.Molecular medicine reports · 2017Article
- Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Hsp90 regulation of fibroblast activation in pulmonary fibrosis.JCI insight · 2017Article
- Unique and Redundant Functions of p70 Ribosomal S6 Kinase Isoforms Regulate Mesenchymal Cell Proliferation and Migration in Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2016Article
- IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function.PloS one · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The p70 ribosomal S6 kinase (S6K) is a downstream substrate that is phosphorylated and activated by the mammalian target of rapamycin complex and regulates multiple cellular processes associated with fibrogenesis. Recent studies demonstrate that aberrant mTORC1-S6K signaling contributes to various pathological conditions, but a direct role in pulmonary fibroproliferation has not been established. Increased phosphorylation of the S6K pathway is detected immediately following transforming growth factor-α (TGF-α) expression in a transgenic model of progressive lung fibrosis. To test the hypothesis that the S6K directly regulates pulmonary fibroproliferative disease we determined the cellular sites of S6K phosphorylation during the induction of fibrosis in the TGF-α model and tested the efficacy of specific pharmacological inhibition of the S6K pathway to prevent and reverse fibrotic disease. Following TGF-α expression increased phosphorylation of the S6K was detected in the airway and alveolar epithelium and the mesenchyme of advanced subpleural fibrotic regions. Specific inhibition of the S6K with the small molecule inhibitor LY-2584702 decreased TGF-α and platelet-derived growth factor-β-induced proliferation of lung fibroblasts in vitro. Administration of S6K inhibitors to TGF-α mice prevented the development of extensive subpleural fibrosis and alterations in lung mechanics, and attenuated the increase in total lung hydroxyproline. S6K inhibition after fibrosis was established attenuated the progression of subpleural fibrosis. Together these studies demonstrate targeting the S6K pathway selectively modifies the progression of pulmonary fibrosis in the subpleural compartment of the lung.
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