ArticleThe Journal of biological chemistry2013
Calreticulin regulates transforming growth factor-β-stimulated extracellular matrix production.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Dihydroartemisinin alleviates pulmonary fibrosis by modulating the calcium signaling pathway in fibroblasts.Journal of translational medicine · 2025Article
- Integrin-Specific Signaling Drives ER Stress-Dependent Atherogenic Endothelial Activation.bioRxiv : the preprint server for biology · 2025Article
- Leveraging Immunogenic Cell Death to Enhance the Immune Response against Malignant Pleural Mesothelioma Tumors.Journal of the American Chemical Society · 2025Article
- Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2025Article
- CaBiomolecules · 2024Review
- Immunomodulation of wound healing leading to efferocytosis.Smart medicine · 2024Review
- Understanding the impact of ER stress on lung physiology.Frontiers in cell and developmental biology · 2024Review
- Article
- Collagen VII maintains proteostasis in dermal fibroblasts by scaffolding TANGO1 cargo.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Thrombospondin-1 Signaling Through the Calreticulin/LDL Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma.Frontiers in cell and developmental biology · 2022Review
- Efferocytosis of vascular cells in cardiovascular disease.Pharmacology & therapeutics · 2022Review
- AAV-mediated expression of NFAT decoy oligonucleotides protects from cardiac hypertrophy and heart failure.Basic research in cardiology · 2021Article
- FK506-Binding Protein 13 Expression Is Upregulated in Interstitial Lung Disease and Correlated with Clinical Severity. A Potentially Protective Role.American journal of respiratory cell and molecular biology · 2021Article
- Roles of Calreticulin in Protein Folding, Immunity, Calcium Signaling and Cell Transformation.Progress in molecular and subcellular biology · 2021Article
- Calreticulin is important for the development of renal fibrosis and dysfunction in diabetic nephropathy.Matrix biology plus · 2020Article
- Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.Circulation research · 2020Review
- The ageing lung under stress.European respiratory review : an official journal of the European Respiratory Society · 2020Review
- Intracellular signaling dynamics and their role in coordinating tissue repair.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Endoplasmic Reticulum Stress Regulates Scleral Remodeling in a Guinea Pig Model of Form-Deprivation Myopia.Journal of ophthalmology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Endoplasmic reticulum (ER) stress is an emerging factor in fibrotic disease, although precise mechanisms are not clear. Calreticulin (CRT) is an ER chaperone and regulator of Ca(2+) signaling up-regulated by ER stress and in fibrotic tissues. Previously, we showed that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). To determine the role of CRT in ECM regulation under fibrotic conditions, we asked whether CRT modified cellular responses to the pro-fibrotic cytokine, TGF-β. These studies show that CRT-/- mouse embryonic fibroblasts (MEFs) and rat and human idiopathic pulmonary fibrosis lung fibroblasts with siRNA CRT knockdown had impaired TGF-β stimulation of type I collagen and fibronectin. In contrast, fibroblasts with increased CRT expression had enhanced responses to TGF-β. The lack of CRT does not impact canonical TGF-β signaling as TGF-β was able to stimulate Smad reporter activity in CRT-/- MEFs. CRT regulation of TGF-β-stimulated Ca(2+) signaling is important for induction of ECM. CRT-/- MEFs failed to increase intracellular Ca(2+) levels in response to TGF-β. NFAT activity is required for ECM stimulation by TGF-β. In CRT-/- MEFs, TGF-β stimulation of NFAT nuclear translocation and reporter activity is impaired. Importantly, CRT is required for TGF-β stimulation of ECM under conditions of ER stress, as tunicamycin-induced ER stress was insufficient to induce ECM production in TGF-β stimulated CRT-/- MEFs. Together, these data identify CRT-regulated Ca(2+)-dependent pathways as a critical molecular link between ER stress and TGF-β fibrotic signaling.
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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.