Search Results (334)

Objective: This study aims to investigate the role of thrombospondin-1 (THBS1) in polycystic ovary syndrome (PCOS) pathogenesis and its mechanism in regulating granulosa cell (GC) function. Methods: Follicular fluid and granulosa cells from 21 PCOS patients and 21 age-matched non-PCOS controls were analysed for THBS1 expression and clinical correlations. A dehydroepiandrosterone (DHEA)-induced PCOS rat model with adeno-associated virus serotype 9 (AAV9)-mediated THBS1 knockdown was used to assess phenotypic changes. The KGN human granulosa-like cell line was employed to evaluate THBS1 overexpression effects on proliferation, apoptosis, and steroidogenesis. Mechanistic studies included RNA sequencing with Gene Set Enrichment Analysis (GSEA), co-immunoprecipitation, molecular docking against the latent TGF-β1 crystal structure (PDB 9VJJ), molecular dynamics simulation, an active/total TGF-β1 ELISA, and pharmacological TGF-β receptor inhibition. Results: THBS1 was elevated in PCOS follicular fluid and granulosa cells and correlated positively with serum AMH and LH after Benjamini–Hochberg FDR correction. AAV9-mediated ovarian THBS1 knockdown (37.4% protein reduction, p = 0.006) ameliorated cystic morphology, restored estrous cyclicity, and normalised serum AMH/LH/T. In KGN cells, THBS1 overexpression suppressed proliferation, induced apoptosis and inflammatory cytokines, and dysregulated steroidogenic enzymes. Transcriptome analysis revealed upregulation of canonical TGF-β/Smad pathway components (SERPINE1, SMAD7, TGFB2, INHBA, CCN2, COL1A1/2). Molecular docking and 100-ns dynamics simulation supported a stable interaction between THBS1 and latent TGF-β1 (ΔG_TOTAL ≈ −120 kcal·mol⁻¹). Co-immunoprecipitation confirmed physical association in cells, and ELISA showed elevated TGF-β1 in PCOS follicular fluid and rat serum, both attenuated by THBS1 knockdown. Pharmacological TGF-β receptor inhibition with SB-431542 rescued THBS1-induced cellular dysfunction. Conclusions: THBS1 is associated with PCOS-related granulosa cell dysfunction through the TGF-β/Smad pathway and represents a candidate biomarker and exploratory therapeutic target that warrants validation in independent multicentre cohorts. Full article

Osteoporosis (OP) is a highly prevalent age-associated inflammatory bone disease that remains underdiagnosed and undertreated despite its substantial global burden. OP is characterized by impaired osteoblast (OB) function, alterations in the extracellular matrix and chronic, low-grade inflammation associated with aging (‘inflammaging’). Initial evidence suggests that the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP) may contribute to disease progression. Additionally, growing evidence indicates a close relationship between osteogenesis and angiogenesis in OP. This study aimed to characterize senescence-associated secretory changes in primary human OBs from donors with OP and to assess their functional impact on endothelial cell behavior. Primary human OBs from donors with OP (n = 15; female: 9, male: 6) and without OP (n = 21; female: 14, male: 7) were analyzed for senescence-associated secretory profiles using ELISA, proteome arrays, and Western blot analysis. The effects of OB-conditioned media on endothelial cell behavior were assessed in endothelial cell migration assays. OBs from donors with OP showed a tendency toward increased senescence-associated features in the β-galactosidase assay, alongside an altered secretory phenotype characterized by increased IL-6, reduced IL-8 and angiogenin levels and decreased expression of extracellular matrix-associated proteins, such as osteopontin, osteonectin, progranulin and thrombospondin-1. Conditioned media from OBs from donors with OP significantly enhanced endothelial cell migration and proliferation in vitro. These findings suggest that OBs from donors with OP exhibit a SASP that may alter the angiogenic microenvironment in the bone. Full article

Myalgic Encephalomyelitis (ME) is a chronic, multisystem disease characterized by systemic metabolic dysfunction and post-exertional malaise (PEM). In this study, we investigated the dysregulation of irisin, an exercise-induced myokine, and its potential antagonism by thrombospondin-1 (TSP-1). In a cross-sectional study (92 ME patients vs. 44 sedentary healthy controls), plasma irisin and TSP-1 levels were measured at baseline and after a 90 min mechanical stress challenge applied to induce PEM. ME patients exhibited significantly lower baseline irisin (p < 0.05) and a blunted exertional response (p < 0.05). Paradoxically, baseline irisin was an independent predictor of fatigue severity (β = 0.728, p = 0.018), with moderate-to-severe patients showing elevated levels of both irisin and TSP-1 (p < 0.05), suggesting a compensatory but ineffective response. Functional cellular dielectric spectroscopy indicated that TSP-1 inhibits irisin signaling in a concentration-dependent manner. Irisin signaling was markedly reduced by both αvβ5 blockade and HSP90α inhibition in this experimental system, consistent with a diminished ability to counteract TSP-1. Collectively, these findings support a model in which dysregulation of the irisin–TSP-1 axis contributes to metabolic dysfunction in ME. Elevated circulating TSP-1 levels are associated with symptom severity and are linked to impaired irisin signaling in an HSP90α- and αvβ5-dependent context. This interaction is consistent with defective metabolic adaptation and highlights a potential therapeutic target that warrants further validation to restore energy homeostasis. Full article

As stem cell therapy in regenerative medicine becomes more socially accepted, human perinatal tissue is attracting attention as a source because it can be harvested non-invasively. Human placental extracts (HPEs), which are prepared using acid hydrolysis and autoclaving, have been approved for treating menopausal disorders and liver dysfunction. This study investigated a new HPE formulation prepared under milder conditions by omitting acid hydrolysis and autoclaving to improve its effectiveness. The new HPE contains relatively high-molecular-weight proteins, including high levels of thioredoxin-1, as well as primarily extracellular matrix proteins such as thrombospondin-1. These proteins appear to be intact or partially fragmented, but they can still potentially maintain their domain structure. The HPE showed both antioxidant and neurite outgrowth activities in a neuronal cell line SH-SY5Y. In a mouse model of hair graying caused by X-ray irradiation, multiple administration of the HPE significantly reduced it. Additionally, the HPE, but not heat-inactivated HPE, alleviated the mechanical allodynia in a mouse model with chemotherapy-induced peripheral neuropathy. Due to the fact that HPE can be produced non-invasively in large quantities in a short time without the need for culturing, the new HPE may have the potential to be an effective and feasible therapy via multiple mechanisms. Full article

Background and Objective: Active surveillance (AS) describes the active monitoring of men with low- to intermediate-risk prostate cancer (PCa), before active management (AM) is needed due to disease progression. A substantial proportion of patients require a transition to AM within a few years of diagnosis. Proclarix is a blood-based diagnostic test that predicts clinically significant PCa (csPCa) and the Proclarix risk score has been shown to correlate with tumor aggressiveness. This study aimed to assess whether Proclarix can predict the likelihood of transition from AS to AM and to compare it to PSA density (PSAD). Methods: We retrospectively evaluated the Proclarix risk scores in serum samples from a Danish cohort of 132 men recruited from the PerPros prostate biobank. Most participants had low- to intermediate-risk PCa and were considered eligible for AS at diagnosis. Blood samples were collected before the initial biopsies, and clinical follow-up data were available for every patient for a minimum of 3 and up to 9.5 years. The primary endpoint was the ability of the Proclarix risk score to predict the transition from AS to AM. The secondary endpoint was to assess whether Proclarix could identify patients at risk of progression to csPCa. For both endpoints, PSA density was also included in the analysis for comparison. Results: Overall, 48 of 132 men (36%) transitioned from AS to AM during follow-up. A baseline Proclarix risk score of ≥50% was associated with a 79% estimated cumulative probability of switching to AM (HR = 4.4, 95% CI: 2.3–8.3, p < 0.001), compared to the 58% (HR = 3.1, 95% CI: 1.7–5.7, p < 0.001) for PSAD At the 5-year follow-up, 82% of men with a Proclarix score ≥ 50% and 57% with PSAD ≥ 0.15 ng/mL/cm³ had progressed to AM. Additionally, 67% and 54% of men showed progression to csPCa with, respectively, Proclarix and PSAD at the confirmatory biopsy. In contrast, among men with a Proclarix score < 50%, only 28% progressed to AM and 32% to csPCa, whereas for PSAD < 0.15 ng/mL/cm³, 17% transitioned to AM and 23% progressed to csPCa. Conclusions: The Proclarix risk score may support clinical decision-making in AS by identifying patients at higher risk of progression and informing follow-up intensity. However, the results should be confirmed in a larger prospective study. Full article

Maternal infection (MI) can increase the risk of neurodevelopmental and behavioural changes. This study examined MI-induced changes in motor coordination through the inflammatory-pathway-mediated epigenetic status of Reln. On gestational day (GD) 10, rats were assigned as (i) Control (Ctrl); (ii) Cronobacter sakazakii (CS) infection on GD-10 through recto-vaginal colonization; (iii) Negative Control (NC) [infected with C. sakazakii and treated with dimethyl sulfoxide (DMSO) 1 h before and 24 h after infection]; and (iv) C. sakazakii-infected rats treated with matrix metalloproteinase inhibitor (MMPI), 1 h before and 24 h after infection (CS + MMPI). Offspring were subjected to footprint analysis and the ladder rung walking test, which revealed that MI caused significant deficits in motor coordination. In addition, MI activated complement components—a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1, C5a)—as well as proinflammatory cytokines such as interleukin-6 (IL-6) and matrix metalloproteinases (MMP-2, MMP-3, and MMP-9). Furthermore, the levels of DNA methyltransferase 3 alpha (DNMT3A), methyl-CpG-binding protein 2 (MeCP2), and histone H3 lysine 4 trimethylation (H3K4me3) were elevated in the CS and NC groups. Concurrently, the level of Reln promoter methylation increased; as a result, mRNA and protein, as well as postsynaptic density protein-95 (PSD-95), levels were decreased. Overall, the findings suggest that MI altered MMP-2/3/9 activity, H3K4me3, and the methylation of Reln, thereby affecting reelin, synaptic protein expression, and motor coordination in an experimental meningitis rat model. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition resulting from a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency, leading to the accumulation of ultra-large von Willebrand factor (vWF) multimers and widespread microvascular thrombosis. While therapeutic plasma exchange and immunosuppression have significantly improved response, refractory and relapsed disease are significant challenges. N-acetylcysteine (NAC) has emerged as a biologically plausible adjunctive therapy due to its potential to reduce disulfide bonds in vWF multimers. However, its clinical role is unclear. This systematic review aimed to evaluate the clinical evidence regarding the efficacy and safety of N-acetylcysteine in patients with immune-mediated TTP. Methods: We performed a systematic review in accordance with the PRISMA guidelines. PubMed/MEDLINE, Google Scholar, and ClinicalTrials.gov were searched until January 2026. Studies involving patients with immune-mediated TTP treated with NAC were included. Case reports, case series, and observational studies involving patients with immune-mediated TTP treated with NAC were included. Risk of bias was evaluated using adapted quality assessment tools. Results: Sixteen studies encompassing 69 patients met the inclusion criteria. Most reports were case reports or small case series; two were larger observational cohorts. NAC was predominantly used as adjunctive therapy in relapsed or refractory TTP. Dose regimens varied. Platelet recovery following NAC was reported within 1–15 days in responding cases. Predominantly positive haematological responses were observed in small series. Significant heterogeneity in patient populations, timing of initiation, concomitant therapies, and outcome reporting limited causal inference. Conclusions: The current evidence suggests that NAC has a biologically rational and potentially adjunctive value in TTP, particularly in refractory disease or resource-constrained settings. However, current data are largely heterogeneous and derived from low-level evidence. Well-designed prospective studies and randomized controlled trials are needed to determine whether NAC provides significant clinical benefit beyond standard therapy. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families living in the Rio Grande Valley of south Texas. We collected clinical data, biometric measurements, hepatic health assessments using Vibration-Controlled Transient Elastography (VCTE), and depression evaluations determined with the Beck Depression Inventory-II. We estimated the heritability (h²) of MASLD-related measures, depression status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), the AST/ALT ratio, and Vibration-Controlled Transient Elastography measurements. For each gene, we derived a genetic endophenotype representing its expression level. We then performed functional network and gene ontology enrichment analyses to characterize the underlying protein pathways. Results: We observed significant associations between the expression of two genes, Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) (h² = 0.56 [0.45, 0.67]) and ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7) (h² = 0.66 [0.55, 0.77]), with depression and multiple MASLD-related phenotypes. We identified 351 genes with expression levels significantly correlated with one or more MASLD phenotypes and depression. Among these, five genes—ADAMTS7, THRAP3, CHPM4A, RAB9A, and PDIA3—were jointly associated with three phenotypes: AST/ALT, ALT, and Controlled Attenuation Parameter (CAP kPa). Based on the Fisher Combined Test, only THRAP3 (p = 3.0 × 10⁻²) and ADAMTS7 (p = 2 × 10⁻²) were jointly significant for depression (BDI-II) and AST, ALT, AST/ALT ratio, FAST, and CAP (kPa). We present a protein–protein interaction network comprising nodes (proteins) and edges (interactions), and a gene ontology enrichment analysis of cellular components. Discussion: Our findings highlight pleiotropic genes underlying MASLD and depression. Two genes, ADAMTS7 and THRAP3, warrant further investigation as potential targets for therapeutic interventions to manage MASLD and depression among Mexican Americans. These results may improve our understanding of the pathways involved in these two diseases, advance current research, and contribute to improvements in personalized medicine. Conclusion: We identified possible shared gene expression phenotypes linking MASLD and depression, which may provide insight into a common molecular underpinning. Pathway enrichment and gene analysis were used to help refine networks and enhance our understanding of complex gene-environmental interactions and their implications for precision medicine. Full article

Spotted fever group (SFG) rickettsioses are tick-borne infectious diseases caused by more than 30 Rickettsia species. As ticks may harbor and transmit multiple pathogens during a single blood meal, sensitive and specific molecular detection methods are essential for early diagnosis. Conventional nested PCR is commonly used but is time-consuming and prone to cross-contamination due to multiple amplification steps. This study evaluated a dual-target one-step nested PCR assay developed as a rapid alternative to conventional nested PCR for SFG Rickettsia detection. Gene-specific primers targeting the Rickettsia outer membrane protein A (ompA) gene and the 17 kDa antigen gene were designed, with a Plasmodium falciparum thrombospondin-related anonymous protein (TRAP) gene included as an internal amplification control. Primer specificity was verified in silico, and assay performance was assessed using synthetic DNA templates. The dual-target one-step nested PCR achieved detection limits of 10 gene copies for the 17 kDa gene and 1000 gene copies for ompA, compared with 10 and 100,000 gene copies, respectively, using conventional nested PCR. Screening of 184 tick specimens identified one positive sample (0.54%) for the Rickettsia 17 kDa gene. Overall, the dual-target one-step nested PCR demonstrated comparable sensitivity to conventional nested PCR while reducing assay time and contamination risk, indicating its potential as a reliable tool for SFG Rickettsia detection. Full article

Background: Heart failure (HF) is a clinical syndrome that involves multiple interconnected pathways. Circulating biomarkers in HF emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy. The aim of the present study was to evaluate circulating levels of biomarkers in elderly patients with improved HF ejection fraction, previously with left ventricular ejection fraction (LVEF) <40%, after six months of drug therapy optimisation. Methods: We enrolled 100 HFimpEF outpatients. All patients provided medical history and underwent physical examination at baseline and after six months of follow-up. The serum values of circulating biomarkers were assessed with an ELISA test. Proteomic analysis was performed on serum samples collected from a subset of 13 patients at baseline and after six months of follow-up. Results: At follow-up, we observed significant improvements in glycometabolic, renal and inflammatory profiles (p < 0.001). Proteomic analysis revealed selective changes in key cardiovascular (CV)-related proteins, such as insulin-like growth factor-binding protein 4 (IBP4), thrombospondin-4 (TSP4), intercellular adhesion molecule 1 (ICAM1), and syndecan-4 (SDC4). Conclusions: This study demonstrates significant improvements across multiple CV biomarkers after six months of therapy optimisation in HFimpEF patients, providing evidence for comprehensive therapeutic effects targeting inflammation, oxidative stress, neurohormonal activation, and thrombotic risk. Full article

Recent studies have demonstrated that primary cilia not only play a role in cardiovascular development, but also in the progression of acquired heart disease. Their role in atrial fibrillation (AF) is incompletely understood. We hypothesize that there is a causal link between primary cilia genes and the occurrence of AF. We integrated AF GWAS data with various multi-omic datasets—including data on gene expression, DNA methylation, and protein expression quantitative trait loci (eQTL, mQTL, and pQTL)—from human left atrial appendage (LAA) tissues and blood. Genetic variants linked to primary cilia-related genes were used as instrumental variables to explore their causal links to AF, through summary-data-based Mendelian randomization (SMR) and Bayesian colocalization. Single-cell sequencing data were used to analyze the expression of the selected genes across different cell types. The mechanisms by which the selected genes exert their effects were explored using RNA sequencing data, clinical indicators, and immunohistochemical markers from 22 patients without AF from the PREDICT-AF cohort, and 21 patients with paroxysmal AF and 19 patients with persistent AF from the MARK-AF cohort. Through SMR analyses, we established significant associations between predicted CEP68 expression and AF in both blood (OR 1.25; 95% CI 1.18–1.33; false discovery rate (FDR) = 1.81 × 10⁻⁹) and LAA tissue (OR 1.12; 95% CI 1.08–1.16; FDR = 6.18 × 10⁻⁹). Moreover, predicted methylation of CEP68 showed an inverse relationship with AF risk (OR 0.87; 95% CI 0.84–0.90; FDR = 2.55 × 10⁻¹⁵). Colocalization results for CEP68 in both blood and the LAA indicated strong evidence of a shared causal variant. Within single-cell data, compared to the control group, AF patients had higher levels of CEP68 in fibroblasts (p = 0.046). In bulk RNA-seq data, CEP68 expression showed no significant differences among the no AF, paroxysmal AF, and persistent AF groups. CEP68 was positively correlated with the cardiac remodeling marker Thrombospondin-2 in 22 patients without AF from the PREDICT-AF cohort (r = 0.45, p = 0.03). In AF patients from the MARK-AF study, CEP68 was also positively associated with LAVI (r = 0.34, p = 0.03). Collectively, our results support a model in which genetically predicted CEP68 regulation is linked to AF liability and is consistent with fibroblast activation and remodeling-related pathways as potential mediators. Full article

Background/Objectives: Doxorubicin (DOX) is an effective chemotherapeutic agent whose clinical utility is limited by cardiotoxicity. To investigate underlying mechanisms, we employed a multi-omics approach integrating transcriptomics and proteomics, leveraging established mouse models of chronic DOX-induced cardiotoxicity. Methods: Five-week-old male mice received weekly DOX (4 mg/kg) or saline injections for six weeks, with heart tissues harvested 4 days post-treatment. Differentially expressed genes (DEGs) and proteins (DEPs) were identified by bulk RNA-seq and proteomics, validated via qPCR and Western blot, respectively. Key DEPs were validated in plasma samples from DOX-treated breast cancer patients. Additionally, temporal comparison was conducted between DEPs in the mice hearts 4 days and 6 weeks post-DOX. Results: RNA-seq revealed upregulation of stress-responsive genes (Phlda3, Trp53inp1) and circadian regulators (Nr1d1), with downregulation of Apelin and Cd74. Proteomics identified upregulation of serpina3n, thrombospondin-1, and epoxide hydrolase 1. Plasma SERPINA3 concentrations were significantly elevated in breast cancer patients 24 h post-DOX. Gene set enrichment analysis (GSEA) revealed upregulated pathways, including p53 signaling, apoptosis, and unfolded protein response. Integrated omics analysis revealed 2089 gene–protein pairs. GSEA of concordant gene–protein pairs implicated p53 signaling, apoptosis, and epithelial–mesenchymal transition in upregulated pathways, while oxidative phosphorylation and metabolic pathways were downregulated. Temporal comparison with a delayed timepoint (6 weeks post-DOX) uncovered dynamic remodeling of cardiac signaling, with early response dominated by inflammatory and apoptotic responses, and delayed response marked by cell cycle and DNA repair pathway activation. Conclusions: This integrated omics study reveals key molecular pathways and temporal changes in DOX-induced cardiotoxicity, identifying potential biomarkers for future cardioprotective strategies. Full article

This pilot study assessed the effectiveness of the intravitreal dexamethasone implant (Ozurdex) in retinal vein occlusion (RVO) patients and explored potential pre-treatment biomarkers to improve management and prognosis. Eighteen patients with branch RVO (BRVO) and twenty-four with central RVO (CRVO) receiving two intravitreal injections of Ozurdex (at baseline and between 4 and 6 months) were included. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline and after 3, 6, and 12 months. Retinal morphology was assessed using optical coherence tomography (OCT), and serum biomarkers were analyzed by ELISAs. No significant BCVA improvement was observed in RVO patients, while CRT significantly decreased from 3 to 12 months. Patients without defects of the retinal inner layers, ellipsoid zone, and external limiting membrane showed significantly higher BCVA at 6 and 12 months. Both BRVO and CRVO groups demonstrated significant BCVA improvement and CRT reduction at 6 and 12 months, with better outcomes in BRVO patients. These patients exhibited lower baseline serum levels of xanthine oxidase (XO) and thrombospondin-1 (TSP-1), which inversely correlated with BCVA at 12 months. Ozurdex was effective in real-life RVO treatment, particularly in BRVO. Serum XO and TSP-1 may serve as prognostic biomarkers for RVO. Full article

Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1–CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated β-galactosidase activity, and activated phosphorylated ERK1/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD. Full article