ArticleAmerican journal of respiratory cell and molecular biology2010
Phosphatidylinositol-3-kinase/akt regulates bleomycin-induced fibroblast proliferation and collagen production.
Article in American journal of respiratory cell and molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 139 citations in OpenAlex.
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- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Network pharmacology and molecular docking reveal mechanisms of amiodarone-induced pulmonary fibrosis.Scientific reports · 2026Article
- NIR light-propelled Janus Polydopamine@Mesoporous silica gene delivery nanomotor for the enhanced gene treatment of critical limb ischemia.Materials today. Bio · 2025Article
- Pulmonary fibrosis: from mechanisms to therapies.Journal of translational medicine · 2025Review
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- Tumor-Associated Macrophages as Major Immunosuppressive Cells in the Tumor Microenvironment.Cancers · 2024Review
- PTGES is involved in myofibroblast differentiation via HIF-1α-dependent glycolysis pathway.Journal of cellular and molecular medicine · 2024Article
- Dimension reduction, cell clustering, and cell-cell communication inference for single-cell transcriptomics with DcjComm.Genome biology · 2024Article
- Suppression of Ventilation-Induced Diaphragm Fibrosis through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.International journal of molecular sciences · 2024Article
- Ketotifen directly modifies the fibrotic response of human skin fibroblasts.Scientific reports · 2024Article
- The evolution ofEuropean respiratory review : an official journal of the European Respiratory Society · 2024Review
- A narrative review of the role of HDAC6 in idiopathic pulmonary fibrosis.Journal of thoracic disease · 2024Review
- Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study.Biomedicines · 2023Article
- Pharmacotherapy and pulmonary fibrosis risk after SARS-CoV-2 infection: a prospective nationwide cohort study in the United States.Lancet regional health. Americas · 2023Article
- PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo.Cellular & molecular biology letters · 2023Article
- An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
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Abstract
Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis, but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total Akt protein expression but induced phosphorylation of the protein at threonine 308 and serine 473 positions. Inhibition of this phosphorylation by PI3K inhibitors or by dominant-negative Akt (T308A/S473A) expression abrogated the effects of bleomycin on fibroblast proliferation and collagen production, suggesting the role of PI3K/Akt in the fibrogenic process. Activation of PI3K/Akt by bleomycin also led to transcriptional activation and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor, which contributed to the fibroproliferative and collagen-inducing effects of bleomycin. The fibrogenic effects of bleomycin were dependent on ROS generation, particularly superoxide anion and hydrogen peroxide, which were induced by bleomycin. Inhibition of ROS generation by antioxidant enzymes, catalase and superoxide dismutase mimetic MnTBAP, abrogated the fibrogenic effects of bleomycin as well as its induction of PI3K/Akt and HIF-1alpha activation. Together, our results indicate a novel role of PI3K/Akt in fibrogenesis of human lung fibroblasts and its regulation by ROS, which could be exploited for the treatment of pulmonary fibrosis and related disorders.
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