ArticleThe American journal of pathology2012
Low α(2)β(1) integrin function enhances the proliferation of fibroblasts from patients with idiopathic pulmonary fibrosis by activation of the β-catenin pathway.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Advances in the Targeted Drug Delivery System for Renal Fibrosis.International journal of nanomedicine · 2026Review
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- Small-Molecule Activation of Protein Phosphatase 2A Counters Bleomycin-Induced Fibrosis in Mice.ACS pharmacology & translational science · 2023Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Integrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells.European journal of cell biology · 2023Article
- A roadmap for developing and engineeringBiophysics reviews · 2023Review
- Hypoxia enhances IPF mesenchymal progenitor cell fibrogenicity via the lactate/GPR81/HIF1α pathway.JCI insight · 2023Article
- The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation.The Journal of biological chemistry · 2022Review
- A scalable 3D tissue culture pipeline to enable functional therapeutic screening for pulmonary fibrosis.APL bioengineering · 2021Article
- Interactions via αInternational journal of molecular sciences · 2021Article
- Review of Integrin-Targeting Biomaterials in Tissue Engineering.Advanced healthcare materials · 2020Review
- Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through αAmerican journal of respiratory cell and molecular biology · 2020Article
- Kelch-like protein 42 is a profibrotic ubiquitin E3 ligase involved in systemic sclerosis.The Journal of biological chemistry · 2020Article
- Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis.Theranostics · 2020Review
- Glycogen Synthase Kinase-3β Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis.Scientific reports · 2019Article
- Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis.Reproductive medicine and biology · 2018Review
- Discoidin Domain Receptor 2 Signaling Regulates Fibroblast Apoptosis through PDK1/Akt.American journal of respiratory cell and molecular biology · 2018Article
- Extracellular matrix as a driver of progressive fibrosis.The Journal of clinical investigation · 2018Review
- The pronounced high expression of discoidin domain receptor 2 in human interstitial lung diseases.ERJ open research · 2018Article
- Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable fibroproliferative disorder characterized by unrelenting proliferation of fibroblasts and their deposition of collagen within alveoli, resulting in permanently scarred, nonfunctional airspaces. Normally, polymerized collagen suppresses fibroblast proliferation and serves as a physiological restraint to limit fibroproliferation after tissue injury. The IPF fibroblast, however, is a pathologically altered cell that has acquired the capacity to elude the proliferation-suppressive effects of polymerized collagen. The mechanism for this phenomenon remains incompletely understood. Here, we demonstrate that expression of α(2)β(1) integrin, a major collagen receptor, is pathologically low in IPF fibroblasts interacting with polymerized collagen. Low integrin expression in IPF fibroblasts is associated with a failure to induce PP2A phosphatase activity, resulting in abnormally high levels of phosphorylated (inactive) GSK-3β and high levels of active β-catenin in the nucleus. Knockdown of β-catenin in IPF fibroblasts inhibits their ability to proliferate on collagen. Interdiction of α(2)β(1) integrin in control fibroblasts reproduces the IPF phenotype and leads to the inability of these cells to activate PP2A, resulting in high levels of phosphorylated GSK-3β and active β-catenin and in enhanced proliferation on collagen. Our findings indicate that the IPF fibroblast phenotype is characterized by low α(2)β(1) integrin expression, resulting in a failure of integrin to activate PP2A phosphatase, which permits inappropriate activation of the β-catenin pathway.
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Registered trials
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.