ArticleExperimental gerontology2015
Plasminogen activator inhibitor 1, fibroblast apoptosis resistance, and aging-related susceptibility to lung fibrosis.
Article in Experimental gerontology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- IL-17RA/RC blockade modulates the fibrinolytic system and MMP activity in bleomycin-induced pulmonary fibrosis in male mice.Physiological reports · 2026Article
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- Review
- Can Cancer Cell Line In Vitro Radioembolization Model Help to Understand How Beta Radiation Affects Liver Tumor and Improve Treatment Results?International journal of molecular sciences · 2026Article
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Review
- The aging lung: microenvironment, mechanisms, and diseases.Frontiers in immunology · 2024Review
- Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors.Developmental cell · 2023Article
- Long-Term Radiological Pulmonary Changes in Mechanically Ventilated Patients with Respiratory Failure due to SARS-CoV-2 Infection.Biomedicines · 2023Article
- Article
- PAI-1 regulates AT2-mediated re-alveolarization and ion permeability.Stem cell research & therapy · 2023Article
- Review
- PAI-1 regulates AT2-mediated re-alveolarization and ion permeability.Research square · 2023Article
- Impaired autophagy-accelerated senescence of alveolar type II epithelial cells drives pulmonary fibrosis induced by single-walled carbon nanotubes.Journal of nanobiotechnology · 2023Article
- Role of Nasal Fibroblasts in Airway Remodeling of Chronic Rhinosinusitis: The Modulating Functions Reexamined.International journal of molecular sciences · 2023Review
- SimulatedPostepy dermatologii i alergologii · 2022Article
- Contracting scars from fibrin drops.Integrative biology : quantitative biosciences from nano to macro · 2022Article
- RNA Sequencing of Epithelial Cell/Fibroblastic Foci Sandwich in Idiopathic Pulmonary Fibrosis: New Insights on the Signaling Pathway.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disorder with unknown cause and no effective treatment. The incidence of and mortality from IPF increase with age, suggesting that advanced age is a major risk factor for IPF. The mechanism underlying the increased susceptibility of the elderly to IPF, however, is unknown. In this study, we show for the first time that the protein level of plasminogen activator inhibitor 1 (PAI-1), a protease inhibitor which plays an essential role in the control of fibrinolysis, was significantly increased with age in mouse lung homogenate and lung fibroblasts. Upon bleomycin challenge, old mice experienced augmented PAI-1 induction and lung fibrosis as compared to young mice. Most interestingly, we show that fewer (myo)fibroblasts underwent apoptosis and more (myo)fibroblasts with increased level of PAI-1 accumulated in the lung of old than in young mice after bleomycin challenge. In vitro studies further demonstrate that fibroblasts isolated from lungs of old mice were resistant to H2O2 and tumor necrosis factor alpha-induced apoptosis and had augmented fibrotic responses to TGF-β1, compared to fibroblasts isolated from young mice. Inhibition of PAI-1 activity with a PAI-1 inhibitor, on the other hand, eliminated the aging-related apoptosis resistance and TGF-β1 sensitivity in isolated fibroblasts. Moreover, we show that knocking down PAI-1 in human lung fibroblasts with PAI-1 siRNA significantly increased their sensitivity to apoptosis and inhibited their responses to TGF-β1. Together, the results suggest that increased PAI-1 expression may underlie the aging-related sensitivity to lung fibrosis in part by protecting fibroblasts from apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
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.