ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Profibrotic TGFβ responses require the cooperative action of PDGF and ErbB receptor tyrosine kinases.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Disease Mechanisms and Therapeutic Advances in Idiopathic and Progressive Pulmonary Fibrosis: From Approved Drugs to Emerging Strategies.Journal of clinical medicine · 2026Review
- Review
- A miniaturized screening platform to identify novel regulators of extracellular matrix alignment.Cancer research communications · 2022Article
- Smad-dependent pathways in the infarcted and failing heart.Current opinion in pharmacology · 2022Review
- EGFR Signaling in Lung Fibrosis.Cells · 2022Review
- Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure.The Journal of clinical investigation · 2022Article
- The EGFR/ErbB inhibitor neratinib modifies the neutrophil phosphoproteome and promotes apoptosis and clearance by airway macrophages.Frontiers in immunology · 2022Article
- Fibrotic Idiopathic Interstitial Lung Disease: The Molecular and Cellular Key Players.International journal of molecular sciences · 2021Review
- ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation.The Journal of cell biology · 2021Article
- Dissecting the Role of Mesenchymal Stem Cells in Idiopathic Pulmonary Fibrosis: Cause or Solution.Frontiers in pharmacology · 2021Review
- New insights into the pathogenesis of Peyronie's disease: A narrative review.Chronic diseases and translational medicine · 2020Review
- Exposed CendR Domain in Homing Peptide Yields Skin-Targeted Therapeutic in Epidermolysis Bullosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- IPF pathogenesis is dependent upon TGFβ induction of IGF-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Systemically Administered, Target-Specific, Multi-Functional Therapeutic Recombinant Proteins in Regenerative Medicine.Nanomaterials (Basel, Switzerland) · 2020Review
- Pharmacology Study of the Multiple Angiogenesis Inhibitor RC28-E on Anti-Fibrosis in a Chemically Induced Lung Injury Model.Biomolecules · 2019Article
- Identification of differentially expressed genes and signaling pathways using bioinformatics in interstitial lung disease due to tyrosine kinase inhibitors targeting the epidermal growth factor receptor.Investigational new drugs · 2019Article
- Fatty acid synthase is required for profibrotic TGF-β signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.Journal of cellular physiology · 2018Review
- Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling.The Journal of clinical investigation · 2017Article
- PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Transforming growth factor β (TGFβ) has significant profibrotic activity both in vitro and in vivo. This reflects its capacity to stimulate fibrogenic mediators and induce the expression of other profibrotic cytokines such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF/ErbB) ligands. Here we address both the mechanisms by which TGFβ induced ErbB ligands and the physiological significance of inhibiting multiple TGFβ-regulated processes. The data document that ErbB ligand induction requires PDGF receptor (PDGFR) mediation and engages a positive autocrine/paracrine feedback loop via ErbB receptors. Whereas PDGFRs are essential for TGFβ-stimulated ErbB ligand up-regulation, TGFβ-specific signals are also required for ErbB receptor activation. Subsequent profibrotic responses are shown to involve the cooperative action of PDGF and ErbB signaling. Moreover, using a murine treatment model of bleomycin-induced pulmonary fibrosis we found that inhibition of TGFβ/PDGF and ErbB pathways with imatinib plus lapatinib, respectively, not only prevented myofibroblast gene expression to a greater extent than either drug alone, but also essentially stabilized gas exchange (oxygen saturation) as an overall measure of lung function. These observations provide important mechanistic insights into profibrotic TGFβ signaling and indicate that targeting multiple cytokines represents a possible strategy to ameliorate organ fibrosis dependent on TGFβ.
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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.