ArticleMolecular and cellular biology2010
Integrin alpha1beta1 regulates epidermal growth factor receptor activation by controlling peroxisome proliferator-activated receptor gamma-dependent caveolin-1 expression.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Bile canaliculi formation in primary hepatocytes requires α1β1 integrin-dependent adherens junction re-organization.Journal of cell science · 2025Article
- Depleting transforming growth factor beta receptor 2 signalling in the cartilage ofOsteoarthritis and cartilage open · 2023Article
- Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage.Journal of orthopaedic surgery and research · 2023Article
- Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Cooperative signaling between integrins and growth factor receptors in fibrosis.Journal of molecular medicine (Berlin, Germany) · 2021Review
- EGF receptor-mediated FUS phosphorylation promotes its nuclear translocation and fibrotic signaling.The Journal of cell biology · 2020Article
- β1 Integrin regulates adult lung alveolar epithelial cell inflammation.JCI insight · 2020Article
- Role of Caveolin-1 in Diabetes and Its Complications.Oxidative medicine and cellular longevity · 2020Review
- β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.Investigative ophthalmology & visual science · 2017Article
- Caveolins and caveolae in ocular physiology and pathophysiology.Progress in retinal and eye research · 2017Review
- Versatile Functions of Caveolin-1 in Aging-related Diseases.Chonnam medical journal · 2017Review
- Integrins in the Spotlight of Cancer.International journal of molecular sciences · 2016Review
- Serum Metabolite Profiles Are Altered by Erlotinib Treatment and the Integrin α1-Null Genotype but Not by Post-Traumatic Osteoarthritis.Journal of proteome research · 2016Article
- Microparticle-Induced Activation of the Vascular Endothelium Requires Caveolin-1/Caveolae.PloS one · 2016Article
- p47(phox) contributes to albuminuria and kidney fibrosis in mice.Kidney international · 2015Article
- Cell Receptor-Basement Membrane Interactions in Health and Disease: A Kidney-Centric View.Current topics in membranes · 2015Review
- Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling.The Journal of clinical investigation · 2014Article
- An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models.Scientific reports · 2014Article
- Integrins in kidney disease.Journal of the American Society of Nephrology : JASN · 2013Review
- Brief report: enrichment of associations in genes with fibrosis, apoptosis, and innate immunity functions with cardiac manifestations of neonatal lupus.Arthritis and rheumatism · 2012Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Integrin alpha1beta1 negatively regulates the generation of profibrotic reactive oxygen species (ROS) by inhibiting epidermal growth factor receptor (EGFR) activation; however, the mechanism by which it does this is unknown. In this study, we show that caveolin-1 (Cav-1), a scaffolding protein that binds integrins and controls growth factor receptor signaling, participates in integrin alpha1beta1-mediated EGFR activation. Integrin alpha1-null mesangial cells (MCs) have reduced Cav-1 levels, and reexpression of the integrin alpha1 subunit increases Cav-1 levels, decreases EGFR activation, and reduces ROS production. Downregulation of Cav-1 in wild-type MCs increases EGFR phosphorylation and ROS synthesis, while overexpression of Cav-1 in the integrin alpha1-null MCs decreases EGFR-mediated ROS production. We further show that integrin alpha1-null MCs have increased levels of activated extracellular signal-regulated kinase (ERK), which leads to reduced activation of peroxisome proliferator-activated receptor gamma (PPARgamma), a transcription factor that positively regulates Cav-1 expression. Moreover, activation of PPARgamma or inhibition of ERK increases Cav-1 levels in the integrin alpha1-null MCs. Finally, we show that glomeruli of integrin alpha1-null mice have reduced levels of Cav-1 and activated PPARgamma but increased levels of phosphorylated EGFR both at baseline and following injury. Thus, integrin alpha1beta1 negatively regulates EGFR activation by positively controlling Cav-1 levels, and the ERK/PPARgamma axis plays a key role in regulating integrin alpha1beta1-dependent Cav-1 expression and consequent EGFR-mediated ROS production.
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