ArticleRespiratory research2020
TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling.
Article in Respiratory research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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104 citing papers in PubMed, 162 citations in OpenAlex.
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- Senescence intensifies bleomycin-induced injury in idiopathic pulmonary fibrosis lung epithelial cells.ERJ open research · 2026Article
- Immune modulatory vaccines targeting tumor microenvironment antigens: recent advances in oncology and beyond.Signal transduction and targeted therapy · 2026Review
- Identification of IPF specific genes expressed by lung tissue-derived fibroblasts using next generation sequencing.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026Article
- Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.Biomaterials science · 2026Article
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- Fibroblast-Targeted Nanodelivery Systems: Mechanisms of Collagen Remodeling Regulation and Novel Strategies for Scar Repair.Pharmaceutics · 2026Review
- Nanomedicine for Acute Respiratory Distress Syndrome: From Pathophysiological Mechanisms and Disease Heterogeneity to Precision Therapy.International journal of nanomedicine · 2026Review
- An hiPSC-derived multi-lineage lung model exhibiting proximal-distal epithelial features for modeling pulmonary fibrosis.Frontiers in cell and developmental biology · 2026Article
- Review of Promising Off-Label Use of Deucravacitinib.International journal of molecular sciences · 2025Review
- Integrating Disease Data and Toxicology Studies to Uncover the Mechanisms of Indium Tin Oxide (ITO) Nanoparticle-Induced Pulmonary Fibrosis and Develop an Adverse Outcome Pathway (AOP) Framework.Environment & health (Washington, D.C.) · 2025Article
- Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.bioRxiv : the preprint server for biology · 2025Article
- Single-cell transcriptomic analysis of blood and bronchoalveolar lavage fluid in progressive fibrosing interstitial lung diseases.Scientific reports · 2025Article
- Emerging Concepts in Fibroblast Biology and Progressive Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
- Hematologic and Immunologic Overlap Between COVID-19 and Idiopathic Pulmonary Fibrosis.Journal of clinical medicine · 2025Review
- M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote IL6-dependent fibroblast activation.Cell biomaterials · 2025Article
- Exploring the Causal Relationship Between Immune Cells and Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Analysis.Journal of clinical laboratory analysis · 2025Article
- Regulatory roles of PIWI-interacting RNAs in cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2025Review
44 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease characterized by a progressive decline in lung function. Fibrotic diseases, such as IPF, are characterized by uncontrolled activation of fibroblasts. Since the microenvironment is known to affect cell behavior, activated fibroblasts can in turn activate healthy neighboring cells. Thus, we investigated IPF paracrine signaling in human lung fibroblasts (HLFs) derived from patients with IPF.
methodsPrimary human fibroblast cultures from IPF (IPF-HLF) and control donor (N-HLF) lung tissues were established and their supernatants were collected. These supernatants were then added to N-HLFs for further culture. Protein and RNA were extracted from IPF/ N-HLFs at baseline. Interleukin-6 (IL-6) and TGF-β-related signaling factors (e.g. STAT3, Smad3) were evaluated by western blot and qPCR. IL-6 levels were measured by ELISA. IL-6 signaling was blocked by Tocilizumab (TCZ) (10 ng/ml).
resultsIPF-HLFs were found to significantly overexpress IL-6 receptor (IL-6R), suppressor of cytokine signaling 3 (SOCS3), phospho-STAT3-Y705 and phospho-Smad3 in comparison to N-HLFs (p < 0.05). In addition, they were found to proliferate faster, secrete more IL-6 and express higher levels of the soluble IL-6R. IPF-HLF increased proliferation was inhibited by TCZ. Moreover, IPF-HLF derived supernatants induced both direct and indirect STAT3 activation that resulted in Smad3 phosphorylation and elevated Gremlin levels in N-HLFs. These effects were also successfully blocked by TCZ.
conclusionsIPF-HLF paracrine signaling leads to IL-6R overexpression, which in turn, affects N-HLF survival. The IL-6/STAT3/Smad3 axis facilitates cellular responses that could potentially promote fibrotic disease. This interplay was successfully blocked by TCZ.
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