ArticleThe EMBO journal2024
p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb.
Article in The EMBO journal, 2024. 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.
- Beryllium Sulfate-Induced Cellular Senescence via the IL-6/STAT3 Pathway to Promote Pulmonary Fibrosis.Journal of applied toxicology : JAT · 2026Article
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- Targeting the senescence‒autophagy axis via p16Signal transduction and targeted therapy · 2026Article
- Urinary detection of therapy-induced senescence and fibrosis using an injectable albumin-based nanoprobe.Nature aging · 2026Article
- Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis.Cells · 2026Article
- p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy.Cell death & disease · 2026Article
- Quercetagetin-rich flavonoids from marigold induce apoptosis inhibit metastasis of non-small cell lung cancer via the p53/p21 signaling pathway.Frontiers in oncology · 2026Article
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Repair and regeneration across the lifespan: an ontogenetic perspective.Frontiers in aging · 2026Review
- Transcriptional regulatory network analysis uncovers modular gene control and potential key regulators in diabetic cardiomyopathy.Frontiers in cell and developmental biology · 2026Article
- Immune surveillance of senescent cells in aging and disease.Nature aging · 2025Review
- Identification and validation of biomarkers related to ferroptosis in idiopathic pulmonary fibrosis.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Fibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis. Moreover, inducible p21 silencing during fibrosis development alleviates disease pathology, decreasing the inflammatory response and ECM accumulation in the lung, and reducing the amount of senescent cells. Furthermore, p21 silencing limits fibrosis progression even when introduced during disease development. These findings show that one common mechanism regulates both cell cycle progression and expression of ECM components, and suggest that targeting p21 might be a new approach for treating age-related fibrotic pathologies.
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