ArticleJCI insight2022
Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2.
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 62 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
62 citing papers in PubMed, 77 citations in OpenAlex.
- Solute Carrier Family 1 Member 5 (SLC1A5)-dependent glutamine transport regulates macrophage senescence and efferocytosis during liver regeneration.Molecular biomedicine · 2026Article
- Context-dependent duality of senescent cells in liver fibrosis.Liver research (Beijing, China) · 2026Review
- Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response.International journal of molecular sciences · 2026Review
- KDM6A/MMP-3 epigenetic axis governs macrophage senescence after spinal cord injury for mediating the regenerative niche to promote neurological repair.Journal of advanced research · 2026Article
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- Transcription-independent induction of rapid-onset senescence is integral to healing.Nature cell biology · 2026Article
- Review
- Peptide hormones and bile acids shaping immune tolerance of the liver: implications and applications.Protein & cell · 2026Review
- Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits.NPJ systems biology and applications · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Senescent hepatic stellate cells drive inflammation and disease progression in MASH (Review).Experimental and therapeutic medicine · 2026Review
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- Context-Dependent Roles of ANGPTL2-Mediated Inflammaging in Tissue Homeostasis, Pathological Tissue Remodeling, and Longevity.Aging cell · 2026Article
- Liver regeneration: cytokine regulation targeting hepatocytes and beyond.Life medicine · 2026Review
- Computational analysis of CCN1 as a druggable target predicts interactions with bioactive compounds.Scientific reports · 2026Article
- Mouse digit AAV gene delivery into fibroblasts regulates regenerative outcome.Science advances · 2026Article
- Molecular time machines unleashed: small-molecule-driven reprogramming to reverse the senescence.Stem cells translational medicine · 2026Review
- Cellular senescence in liver diseases: From molecular drivers to therapeutic targeting.Journal of hepatology · 2026Review
- Review
- Tubule-derived CCN1 drives renal repair via αCell death & disease · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Senescent cells have long been associated with deleterious effects in aging-related pathologies, although recent studies have uncovered their beneficial roles in certain contexts, such as wound healing. We have found that hepatic stellate cells (HSCs) underwent senescence within 2 days after 2/3 partial hepatectomy (PHx) in young (2-3 months old) mice, and the elimination of these senescent cells by using the senolytic drug ABT263 or by using a genetic mouse model impaired liver regeneration. Senescent HSCs secrete IL-6 and CXCR2 ligands as part of the senescence-associated secretory phenotype, which induces multiple signaling pathways to stimulate liver regeneration. IL-6 activates STAT3, induces Yes-associated protein (YAP) activation through SRC family kinases, and synergizes with CXCL2 to activate ERK1/2 to stimulate hepatocyte proliferation. The administration of either IL-6 or CXCL2 partially restored liver regeneration in mice with senescent cell elimination, and the combination of both fully restored liver weight recovery. Furthermore, the matricellular protein central communication network factor 1 (CCN1, previously called CYR61) was rapidly elevated in response to PHx and induced HSC senescence. Knockin mice expressing a mutant CCN1 unable to bind integrin α6β1 were deficient in senescent cells and liver regeneration after PHx. Thus, HSC senescence, largely induced by CCN1, is a programmed response to PHx and plays a critical role in liver regeneration through signaling pathways activated by IL-6 and ligands of CXCR2.
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Registered trials
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.