ArticlePloS one2014
Cell stress induces upregulation of osteopontin via the ERK pathway in type II alveolar epithelial cells.
Article in PloS one, 2014. 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, 37 citations in OpenAlex.
- Urinary adhesion molecules with ERK signaling as predictive biomarkers for kidney stones: a pilot study.BMC urology · 2026Article
- A Macrophage-Derived Factor on Human iPSC-Derived Cardiomyocyte Function: The Role of Osteopontin.Cells · 2025Article
- Serum osteopontin as a prognostic biomarker in acute exacerbations of chronic obstructive pulmonary disease.Frontiers in immunology · 2025Article
- Inhibition of ERK1/2 signaling prevents bone marrow fibrosis by reducing osteopontin plasma levels in a myelofibrosis mouse model.Leukemia · 2023Article
- ADAM 17 and Epithelial-to-Mesenchymal Transition: The Evolving Story and Its Link to Fibrosis and Cancer.Journal of clinical medicine · 2021Review
- Effects ofFrontiers in pharmacology · 2021Article
- TGF-β Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPβ Pathways.International journal of molecular sciences · 2020Article
- Stimulation of THP-1 Macrophages with LPS Increased the Production of Osteopontin-Encapsulating Exosome.International journal of molecular sciences · 2020Article
- Protective Mechanism and Treatment of Neurogenesis in Cerebral Ischemia.Neurochemical research · 2020Review
- Proteomic and ultrastructural analysis of Clara cell and type II alveolar epithelial cell-type lung cancer cells.Translational cancer research · 2020Article
- Osteopontin Attenuates Secondary Neurodegeneration in the Thalamus after Experimental Stroke.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Bleomycin Inhibits Proliferation via Schlafen-Mediated Cell Cycle Arrest in Mouse Alveolar Epithelial Cells.Tuberculosis and respiratory diseases · 2019Article
- Osteopontin Mediates Cetuximab Resistance via the MAPK Pathway in NSCLC Cells.OncoTargets and therapy · 2019Article
- Bioluminescence imaging visualizes osteopontin-induced neurogenesis and neuroblast migration in the mouse brain after stroke.Stem cell research & therapy · 2018Article
- Osteopontin Expression in Cardiomyocytes Is Increased in Pediatric Patients With Sepsis or Pneumonia.Frontiers in physiology · 2018Article
- Induction of Osteopontin by Dengue Virus-3 Infection in THP-1 Cells: Inhibition of the Synthesis by Brefelamide and Its Derivative.Frontiers in microbiology · 2017Article
- Endoplasmic reticulum stress, a new wrestler, in the pathogenesis of idiopathic pulmonary fibrosis.American journal of translational research · 2017Article
- Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin 1/VASPpS239 Regulates Metastatic Growth and Is Modified by DHA Supplementation.Molecular cancer therapeutics · 2016Article
- Utility of Plasma Osteopontin Levels in Management of Community-Acquired Pneumonia.International journal of medical sciences · 2016Article
- Osteopontin facilitates invasion in human trophoblastic cells via promoting matrix metalloproteinase-9 in vitro.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteopontin (OPN) is a multifunctional protein that plays important roles in cell growth, differentiation, migration and tissue fibrosis. In human idiopathic pulmonary fibrosis and murine bleomycin-induced lung fibrosis, OPN is upregulated in type II alveolar epithelial cells (AEC II). However, the mechanism of OPN induction in AEC II is not fully understood. In this study, we demonstrate the molecular mechanism of OPN induction in AEC II and elucidate the functions of OPN in AEC II and lung fibroblasts. Human lung adenocarcinoma cells (A549) and mouse alveolar epithelial cells (MLE12), used as type II alveolar epithelial cell lines for in vitro assays, and human pulmonary alveolar epithelial cells (HPAEpiC) were treated with either bleomycin, doxorubicin or tunicamycin. The mechanism of OPN induction in these cells and its function as a pro-fibrotic cytokine on A549 and lung fibroblasts were analyzed. The DNA damaging reagents bleomycin and doxorubicin were found to induce OPN expression in A549, MLE12 and HPAEpiC. OPN expression was induced via activation of the extracellular signal-regulated protein kinase (ERK)-dependent signaling pathway in A549 and MLE12. The endoplasmic reticulum (ER) stress-inducing reagent tunicamycin induced OPN mRNA expression in A549, MLE12 and HPAEpiC, and OPN mRNA expression was induced via activation of the ERK-dependent signaling pathway in A549 and MLE12. Another ER stress-inducing reagent thapsigargin induced the expression of OPN mRNA as well as the subsequent production of OPN in A549 and MLE12. Furthermore, OPN promoted the proliferation of A549 and the migration of normal human lung fibroblasts. Inhibition of OPN by small interference RNA or neutralizing antibody suppressed both of these responses. The results of this study suggest that cell stress induces the upregulation of OPN in AEC II by signaling through the ERK pathway, and that upregulated OPN may play a role in fibrogenesis of the lung.
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