ArticleJCI insight2022
Increased expression and accumulation of GDF15 in IPF extracellular matrix contribute to fibrosis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 62 citations in OpenAlex.
- Serum growth differentiation factor 15 as a candidate biomarker associated with interstitial lung disease in primary Sjögren's syndrome: a clinical cross-sectional study.Clinical rheumatology · 2026Article
- GDF15: A Hijacked Metabo-Hormone Orchestrating Cachexia and Immunosuppression in Cancer.Biomolecules · 2026Review
- Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Endothelial GDF15 deficiency enhances barrier function and mitigates pulmonary fibrosis.JCI insight · 2026Article
- FTIR imaging identifies alterations in lung tissue structure and biochemical composition in human idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Prioritizing Therapeutic Targets for Interstitial Lung Disease: A Causal Mediation Analysis.Research square · 2026Article
- Convergent Roles of Growth Differentiation Factor-15 (GDF-15) in Mechanotransduction, Vascular Disorganization, and Immune Suppression in Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Serum proteomics mirrors the histopathological changes underlying different etiologies of primary mitral valve disease.Bioscience reports · 2026Article
- Article
- Crosstalk between TGF-β and Wnt/β-catenin signaling drives fibrogenic and stem-like phenotypes in senescent MDA-MB-231 breast cancer cells.npj aging · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Immunomodulatory functions of growth differentiation factor 15 in skin aging and inflammatory dermatoses.Frontiers in immunology · 2026Review
- A novel agarose-free, standardized generation and versatile ECM characterization of decellularized scaffolds from normal and fibrotic human lung tissue.Frontiers in bioengineering and biotechnology · 2026Article
- A human lung organoid platform for studying radiation-induced pulmonary fibrosis and antifibrotic drug screening.Scientific reports · 2025Article
- Idiopathic Pulmonary Fibrosis: Cellular Heterogeneity, Mechanisms, and Therapeutic Implications.MedComm · 2025Review
- Growth differentiation factor-15 as a non-invasive biomarker of liver fibrosis in sickle cell disease.International journal of hematology · 2025Article
- Single-cell dissection of chronic lung allograft dysfunction reveals convergent and distinct fibrotic mechanisms.JCI insight · 2025Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- Bioinformatics-based identification of mirdametinib as a potential therapeutic target for idiopathic pulmonary fibrosis associated with endoplasmic reticulum stress.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unmet medical need. It is characterized by formation of scar tissue leading to a progressive and irreversible decline in lung function. IPF is associated with repeated injury, which may alter the composition of the extracellular matrix (ECM). Here, we demonstrate that IPF patient-derived pulmonary ECM drives profibrotic response in normal human lung fibroblasts (NHLF) in a 3D spheroid assay. Next, we reveal distinct alterations in composition of the diseased ECM, identifying potentially novel associations with IPF. Growth differentiation factor 15 (GDF15) was identified among the most significantly upregulated proteins in the IPF lung-derived ECM. In vivo, GDF15 neutralization in a bleomycin-induced lung fibrosis model led to significantly less fibrosis. In vitro, recombinant GDF15 (rGDF15) stimulated α smooth muscle actin (αSMA) expression in NHLF, and this was mediated by the activin receptor-like kinase 5 (ALK5) receptor. Furthermore, in the presence of rGDF15, the migration of NHLF in collagen gel was reduced. In addition, we observed a cell type-dependent effect of GDF15 on the expression of cell senescence markers. Our data suggest that GDF15 mediates lung fibrosis through fibroblast activation and differentiation, implicating a potential direct role of this matrix-associated cytokine in promoting aberrant cell responses in disease.
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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.