ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
The vitronectin RGD motif regulates TGF-β-induced alveolar epithelial cell apoptosis.
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 21 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
21 citing papers in PubMed, 35 citations in OpenAlex.
- Degradation of oxidized phospholipids by lysosomal phospholipase A2 regulates pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
- Article
- Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis.The Journal of pathology · 2024Article
- CD36/Lyn kinase interactions within macrophages promotes pulmonary fibrosis in response to oxidized phospholipid.Respiratory research · 2023Article
- Inhibition of discoidin domain receptor 2 reveals kinase-dependent and kinase-independent functions in regulating fibroblast activity.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Pericyte-to-endothelial cell signaling via vitronectin-integrin regulates blood-CNS barrier.Neuron · 2022Article
- Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option.Cells · 2022Review
- Fibrinogen mediates cadmium-induced macrophage activation and serves as a predictor of cadmium exposure in chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?International journal of molecular sciences · 2021Review
- Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through αAmerican journal of respiratory cell and molecular biology · 2020Article
- NADPH Oxidase Inhibition in Fibrotic Pathologies.Antioxidants & redox signaling · 2020Article
- Diverse Injury Pathways Induce Alveolar Epithelial Cell CCL2/12, Which Promotes Lung Fibrosis.American journal of respiratory cell and molecular biology · 2020Article
- PTEN loss regulates alveolar epithelial cell senescence in pulmonary fibrosis depending on Akt activation.Aging · 2019Article
- Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10-dependent sensitization of epithelial cell apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Mechanisms for the Resolution of Organ Fibrosis.Physiology (Bethesda, Md.) · 2019Review
- Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis.Cell death & disease · 2018Article
- Discoidin Domain Receptor 2 Signaling Regulates Fibroblast Apoptosis through PDK1/Akt.American journal of respiratory cell and molecular biology · 2018Article
- Bacterial Outer Membrane Vesicles Induce Vitronectin Release Into the Bronchoalveolar Space Conferring Protection From Complement-Mediated Killing.Frontiers in microbiology · 2018Article
- Focal adhesion kinase signaling determines the fate of lung epithelial cells in response to TGF-β.American journal of physiology. Lung cellular and molecular physiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-β (TGF-β) is a critical driver of acute lung injury and fibrosis. Injury leads to activation of TGF-β, which regulates changes in the cellular and matrix makeup of the lung during the repair and fibrosis phase. TGF-β can also initiate alveolar epithelial cell (AEC) apoptosis. Injury leads to destruction of the laminin-rich basement membrane, which is replaced by a provisional matrix composed of arginine-glycine-aspartate (RGD) motif-containing plasma matrix proteins, including vitronectin and fibronectin. To determine the role of specific matrix proteins on TGF-β-induced apoptosis, we studied primary AECs cultured on different matrix conditions and utilized mice with deletion of vitronectin (Vtn(-/-)) or mice in which the vitronectin RGD motif is mutated to nonintegrin-binding arginine-glycine-glutamate (RGE) (Vtn(RGE/RGE)). We found that AECs cultured on fibronectin and vitronectin or in wild-type mouse serum are resistant to TGF-β-induced apoptosis. In contrast, AECs cultured on laminin or in serum from Vtn(-/-) or Vtn(RGE/RGE) mice undergo robust TGF-β-induced apoptosis. Plasminogen activator inhibitor-1 (PAI-1) sensitizes AECs to greater apoptosis by disrupting AEC engagement to vitronectin. Inhibition of integrin-associated signaling proteins augments AEC apoptosis. Mice with transgenic deletion of PAI-1 have less apoptosis after bleomycin, but deletion of vitronectin or disruption of the vitronectin RGD motif reverses this protection, suggesting that the proapoptotic function of PAI-1 is mediated through vitronectin inhibition. Collectively, these data suggest that integrin-matrix signaling is an important regulator of TGF-β-mediated AEC apoptosis and that PAI-1 functions as a natural regulator of this interaction.
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.