ArticleJCI insight2022
Single-cell analysis of senescent epithelia reveals targetable mechanisms promoting fibrosis.
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 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- The vicious cycle of SASP and inflammaging promotes aging and age-related diseases.Communications biology · 2026Review
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- DNA hypermethylation of FGFR2 drives fibrosis in the aging kidney.Scientific reports · 2026Article
- Targeting cellular senescence in diabetic kidney disease: potential of regenerative, cell-based therapies and other senotherapeutic approaches.Kidney international · 2026Review
- Fisetin as a nutritional senotherapeutic: mechanisms, translational promise, and lessons from chronic kidney disease.Frontiers in nutrition · 2026Review
- Interpretable Machine Learning Identifies Hub Biomarkers of Renal Fibrosis and Their Potential Medical Applications.Drug design, development and therapy · 2026Article
- Single Cell and Spatial Transcriptomics Define a Proinflammatory and Profibrotic Niche After Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of matrix metalloproteinase-9 attenuates kidney fibrosis and cellular senescence in the transition from acute kidney injury to chronic kidney disease.Renal failure · 2025Article
- Inhibition of MCL-1 to eliminate senescent cells and mitigate renal fibrosis in aristolochic acid nephropathy.Cell death & disease · 2025Article
- Noncanonical function of Pannexin1 promotes cellular senescence and renal fibrosis post-acute kidney injury.Nature communications · 2025Article
- Mechanisms of Acute Kidney Injury-Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities.Biomolecules · 2025Review
- Deletion of Pyruvate Carboxylase in Tubular Epithelial Cell Promotes Renal Fibrosis by Regulating SQOR/cGAS/STING-Mediated Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule.The American journal of pathology · 2025Review
- LAPTM5: A Novel Target in an Old Fight against Tubular Senescence.Journal of the American Society of Nephrology : JASN · 2024Article
- Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.Nature cell biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
Progressive fibrosis and maladaptive organ repair result in significant morbidity and millions of premature deaths annually. Senescent cells accumulate with aging and after injury and are implicated in organ fibrosis, but the mechanisms by which senescence influences repair are poorly understood. Using 2 murine models of injury and repair, we show that obstructive injury generated senescent epithelia, which persisted after resolution of the original injury, promoted ongoing fibrosis, and impeded adaptive repair. Depletion of senescent cells with ABT-263 reduced fibrosis in reversed ureteric obstruction and after renal ischemia/reperfusion injury. We validated these findings in humans, showing that senescence and fibrosis persisted after relieved renal obstruction. We next characterized senescent epithelia in murine renal injury using single-cell RNA-Seq. We extended our classification to human kidney and liver disease and identified conserved profibrotic proteins, which we validated in vitro and in human disease. We demonstrated that increased levels of protein disulfide isomerase family A member 3 (PDIA3) augmented TGF-β-mediated fibroblast activation. Inhibition of PDIA3 in vivo significantly reduced kidney fibrosis during ongoing renal injury and as such represented a new potential therapeutic pathway. Analysis of the signaling pathways of senescent epithelia connected senescence to organ fibrosis, permitting rational design of antifibrotic therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.