ArticleInternational journal of radiation oncology, biology, physics2021
IGF-1 Receptor Signaling Regulates Type II Pneumocyte Senescence and Resulting Macrophage Polarization in Lung Fibrosis.
Article in International journal of radiation oncology, biology, physics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- RNA Modifications as Molecular Regulators of Alveolar Epithelial Injury and Aberrant Repair in Pulmonary Fibrosis.Biomolecules · 2026Review
- Methyl Quercetin Inhibits Radiation-induced Senescence and TGF-β1-induced Myofibroblast Differentiation Through psmad3/TGF-β Signaling.Radiation research · 2026Article
- LncRNA TUG1 promotes hypertrophic scar formation via the miR-627/IGF1R axis.Journal of molecular histology · 2026Article
- Profibrotic macrophage populations and cell communications in pulmonary fibrosis.Journal of physiology and biochemistry · 2026Review
- Airway injury induces alveolar epithelial responses mediated by macrophages.Cell reports · 2026Article
- Breast cancer radiotherapy and the risk of lung injury: Advances and perspectives.Advances in radiotherapy & nuclear medicine · 2026Article
- TMEM131-Mediated Soluble TRAIL Triggered Type II Alveolar Epithelial Cell Senescence in Radiation-Induced Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MIF/CD74 axis regulates alveolar epithelial type II cell apoptosis, autophagy, and transdifferentiation in bronchopulmonary dysplasia via the TGFβ1/SMAD4 pathway.Respiratory research · 2025Article
- IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.Respiratory research · 2025Article
- Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.International journal of oral science · 2025Review
- The tumor microenvironment of metastatic osteosarcoma in the human and canine lung.Communications biology · 2025Review
- Hedgehog-interacting protein orchestrates alveologenesis and protects against bronchopulmonary dysplasia and emphysema.Science advances · 2025Article
- Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation.Materials today. Bio · 2025Article
- Macrophages and Pulmonary Fibrosis.Current molecular medicine · 2025Review
- Review
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Targeting senescence-associated secretory phenotypes to remodel the tumour microenvironment and modulate tumour outcomes.Clinical and translational medicine · 2024Review
- TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.Respiratory research · 2024Article
- The role of macrophage polarization and cellular crosstalk in the pulmonary fibrotic microenvironment: a review.Cell communication and signaling : CCS · 2024Review
- Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.Molecular medicine (Cambridge, Mass.) · 2023Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeType II pneumocyte (alveolar epithelial cells type II [AECII]) senescence has been implicated in the progression of lung fibrosis. The capacity of senescent cells to modulate pulmonary macrophages to drive fibrosis is unexplored. Insulin-like growth factor-1 receptor (IGF-1R) signaling has been implicated as a regulator of senescence and aging. METHODS AND MATERIALS: Mice with an AECII-specific deletion of IGF-1R received thoracic irradiation (n ≥ 5 per condition), and the effect of IGF-1R deficiency on radiation-induced AECII senescence and macrophage polarization to an alternatively activated phenotype (M2) was investigated. IGF-1R signaling, macrophage polarization, and senescence were evaluated in surgically resected human lung (n = 63).
resultsIGF-1R deficient mice demonstrated reduced AECII senescence (senescent AECII/field; intact: 7.25% ± 3.5% [mean ± SD], deficient: 2.75% ± 2.8%, P = .0001), reduced accumulation of M2 macrophages (intact: 24.7 ± 2.2 cells/field, deficient: 15.5 ± 1.2 cells/field, P = .0086), and fibrosis (hydroxyproline content; intact: 71.9 ± 21.7 μg/lung, deficient: 31.7 ± 7.9, P = .0485) after irradiation. Senescent AECII enhanced M2 polarization in a paracrine fashion (relative Arg1 mRNA, 0 Gy: 1.0 ± 0.4, 17.5 Gy: 7.34 ± 0.5, P < .0001). Evaluation of surgical samples from patients treated with chemoradiation demonstrated increased expression of IGF-1 (unirradiated: 10.2% ± 4.9% area, irradiated: 15.1% ± 11.5%, P = .0377), p21 (unirradiated: 0.013 ± 0.02 histoscore, irradiated: 0.084 ± 0.09 histoscore, P = .0002), IL-13 (unirradiated: 13.7% ± 2.8% area, irradiated: 21.7% ± 3.8%, P < .0001), and M2 macrophages in fibrotic regions relative to nonfibrotic regions (unirradiated: 11.4 ± 12.2 CD163 + cells/core, irradiated: 43.1 ± 40.9 cells/core, P = .0011), consistent with findings from animal models of lung fibrosis.
conclusionsThis study demonstrates that senescent AECII are necessary for the progression of pulmonary fibrosis and serve as a targetable, chronic stimuli for macrophage activation in fibrotic lung.
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