ArticleGeroScience2025
Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.
Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- From Mechanical Cues to Lung Injury: Mapping the Global Landscape and Frontiers of Mechanoregulation Through Bibliometrics and LDA Analysis.Journal of cellular and molecular medicine · 2026Article
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Substrate Stiffness and Viscoelasticity Influence Fibroblast Senescence.Journal of biomedical materials research. Part A · 2026Article
- Dynamic tRNA modification landscapes reveal METTL1 in fibroblasts as a central regulator of aging.Science China. Life sciences · 2026Article
- Substrate stiffness dictates unique paths towards proliferative arrest in WI-38 cells.GeroScience · 2026Article
- Effects of Aerosol Extract From Heated Tobacco Products on Senescence-Associated Gene Expression in Human Lung Fibroblasts.Geriatrics & gerontology international · 2026Article
- The Role of Cellular Senescence in Oral Health and Disease.International journal of molecular sciences · 2026Review
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy-Induced Senescent Cells.Aging cell · 2026Article
- Why and How Are Infants with Hutchinson-Gilford Progeria Syndrome Born Without Severe Manifestations?Medical sciences (Basel, Switzerland) · 2025Review
- Spatial Mass Spectrometry-Based Proteomic Analysis of Normal-Appearing Glomeruli from Young and Old Adults.Kidney360 · 2025Article
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Involvement of SIRT1-mediated aging in liver diseases.Frontiers in cell and developmental biology · 2025Review
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18 authors.
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Abstract
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-β-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (approximately 3 GPa) substrates, followed by senescence induction using doxorubicin, we identified unique high-stiffness-driven secretory protein profiles using mass spectrometry and transcriptomic signatures, both showing an enrichment in collagen proteins. Consistently, clusters of p21 + cells are seen in fibrotic regions of bleomycin induced pulmonary fibrosis in mice. Computational meta-analysis of single-cell RNA sequencing datasets from human interstitial lung disease confirmed these stiffness SASP genes are highly expressed in disease fibroblasts and strongly correlate with mechanotransduction and senescence-related pathways. Thus, mechanical forces shape cell senescence and their secretory phenotypes.
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