Ask about this productRelated genes to: CDH5 Blocking Peptide
- Gene:
- CDH5 NIH gene
- Name:
- cadherin 5
- Previous symbol:
- -
- Synonyms:
- 7B4, CD144
- Chromosome:
- 16q21
- Locus Type:
- gene with protein product
- Date approved:
- 1992-11-20
- Date modifiied:
- 2016-10-05
Related products to: CDH5 Blocking Peptide
Related articles to: CDH5 Blocking Peptide
- Endothelial dysfunction is a critical determinant of sepsis-associated organ injury, often driven by its interaction with overactivated immune cells. Neutrophils, the dominant early responders in sepsis, contribute to endothelial barrier disruption, yet the underlying metabolic and epigenetic mechanisms remain poorly understood. Here, we observed elevated intracellular lactate levels in neutrophils from septic patients which correlated with organ dysfunction and systemic inflammatory markers. Mechanistically, lactate-induced histone H3K18 lactylation (H3K18la) enhanced (autophagy related 7) transcription, initiating a non-degradative, secretory autophagy program. This facilitated the extracellular release of IL1B/IL-1B (interleukin 1 beta), a key driver of endothelial dysfunction. Interference of lactate production, ATG7 expression or IL1B signaling alleviated endothelial dysfunction . , myeloid-specific deletion of the lactylation writer EP300/p300 (EP300 lysine acetyltransferase) mitigated pulmonary endothelial dysfunction and lung injury. Additionally, the stress-responsive transcription factor ATF4/CREB-2 (activating transcription factor 4) was found to directly interact with both EP300 and H3K18la, amplifying H3K18la-driven transcription. Our findings uncover a metabolically driven, epigenetically regulated secretory autophagy pathway in neutrophils that mediates endothelial dysfunction. Our study provides mechanistic insights into neutrophil-endothelial crosstalk in sepsis and identifies EP300, ATG7, and IL1B as potential therapeutic targets for sepsis. ALI: acute lung injury; ANOVA: analysis of variance; ATF4/CREB-2: activating transcription factor 4; ATG7/GSA7: autophagy related 7; ATP: adenosine triphosphate; BafA1: bafilomycin A; BMDN: bone marrow-derived neutrophil; C-CASP1: cleaved-caspase 1; CDH5/CD144: cadherin 5; CRP/PTX1: C-reactive protein; CST3: cystatin C; CXCL8/IL-8: C-X-C motif chemokine ligand 8; DAPI: 4',6-diamidino-2-phenylindole; DEG: differentially expressed gene; dHL-60: dimethyl sulfoxide-differentiated HL-60 cell; DMSO: dimethyl sulfoxide; ELISA: enzyme-linked immunosorbent assay; EP300/p300: EP300 lysine acetyltransferase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic - pyruvic transaminase; GSDMD-N: gasdermin D N-terminal; H&E: hematoxylin and eosin; H3K18la: histone H3K18 lactylation; HRP: horseradish peroxidase; ICU: intensive care unit; IHC: immunohistochemistry; IL1B/IL-1B: interleukin 1 beta; IL1R1/CD121A: interleukin 1 receptor type 1; IL6/IL-6: interleukin 6; KEGG: Kyoto Encyclopedia of Genes and Genomes; LAMP1/CD107a: lysosome associated membrane protein 1; LDHA: lactate dehydrogenase A; LPS: lipopolysaccharide; 3-MA: 3-methyladenine; NLRP3/NALP3: NLR family pyrin domain containing 3; PBS: phosphate-buffered saline; PCT: procalcitonin; PMN: peripheral neutrophils; Rapa: rapamycin; RNA-seq: RNA-sequencing; SERPINE1/PAI1: serpin family E member 1; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; SOFA: Sequential Organ Failure Assessment; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TNF/TNF-alpha: tumor necrosis factor; panKla: pan-histone lactylation; VCAM1/CD106: vascular cell adhesion molecule 1. - Source: PubMed
Publication date: 2026/06/12
Li YinjiaozhiLi RanranZhu DehaoTian RuiChen YangWang XiaoliLi LeiPan TingtingTan RuomingQu Hongping - Ischemic stroke remains a leading cause of disability and mortality worldwide, with limited acute therapeutic options. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates endothelial function, vascular integrity, and immune responses, and reduced circulating S1P levels have been reported in ischemic stroke. Whether plasma S1P depletion parallels alterations in brain-endothelial S1P metabolism, receptor expression, and endothelial activation, however, remains unclear. Here, we characterized circulating S1P levels together with stroke-associated changes in brain-endothelial S1P pathway expression, markers related to endothelial activation, and blood-brain barrier (BBB) integrity. - Source: PubMed
Publication date: 2026/06/12
Porschen Lisa TMatthes FrankMatuskova HanaBraadt LinoPetzold Gabor CLindgren Arne GMeissner Anja - Carotid intima-media thickening (IMT) is a major risk factor for cardiovascular disease (CVD). The large ribosomal subunit protein 17 (Rpl17) was recently reported as a CVD-associated gene; however, ribosomal mutations generally are not associated with vascular dysfunction. We have created a novel genetic model of decreased RpL17 in endothelial cells (EC) to determine how changes in endothelial ribosome expression cause IMT. - Source: PubMed
Publication date: 2026/05/25
Wines-Samuelson MaryChowdhury SayantaniSenchanthisai SharonShaposhnikov MichalSowden MarkBerk Bradford C - Genome-wide association studies (GWAS) link the Tropomyosin 1 (Tpm1) locus to quantitative blood trait variation, but related mechanisms are unclear. Tpm1 encodes an actin-binding protein that regulates actin filament diversity, cell adhesion, signaling, and actomyosin contractility. Murine Tpm1 deficiency enhances hemogenic endothelial cell (HEC) specification, but it was unclear if these effects extended to postnatal hematopoiesis. We used Cdh5 and Vav models to conditionally knock out Tpm1 (Tpm1KO) in endothelial anor hematopoietic cells. Both models ablate Tpm1 in postnatal blood. Endothelial Tpm1KO increases HEC specification without altering hematopoietic progenitor cell production or adult blood counts, suggesting separate roles for Tpm1 in the embryonic and adult blood systems. Tpm1KO increases adult platelet lifespan and diminishes adhesion to fibronectin and fibrinogen. Chemical Tpm1 inhibition also reduces focal adhesion in murine and human platelets. Altered platelet morphology and reduced platelet spreading suggest perturbed actomyosin contractility underlies these findings. Platelet fibrin binding promotes blood clot contraction, which reduces occlusive thrombosis. Tpm1KO limits clot contraction and worsens vascular occlusion in ferric chloride-induced stroke models. In addition to offering a mechanistic explanation for why genetic variation at the TPM1 alters platelet traits in GWAS, our findings reveal novel roles for Tpm1 in clot contraction and thrombosis. - Source: PubMed
Publication date: 2026/06/04
Kung Po-LunTsao VictorPeshkova Alina DMarcos-Contreras Oscar AHa KimDulmovits Brian MOkoli NkemdilimSinha AnviFonar GennadiyQiu RongBates Rolf DYeboah JanelleShalaby CarsonTruex TylerJeong SoominHardeman Edna CGunning Peter WMuzykantov Vladimir RMyerson Jacob WThom Christopher S - Genome-wide association studies have identified rare and common mutations associated with increased risk of pulmonary arterial hypertension (PAH), but the mechanism by which impaired SOX17 expression increases PAH risk is not known. Notably, SOX17 plays a critical role in endothelial identity during development by suppressing RUNX1 through binding to its promoter and directing stem and progenitor cells toward an endothelial rather than a hematopoietic cell fate. RUNX1 functions as a key regulator of myeloid differentiation, aberrant angiogenesis and adverse cardiac remodeling. Previously, we found that RUNX1 inhibition reverses pulmonary hypertension (PH) in multiple animal models. Here, we hypothesize that impaired expression of SOX17 in PAH leads to endothelial cell (EC) dysfunction by failing to suppress RUNX1. - Source: PubMed
Publication date: 2026/05/15
Akosman BediaChoi Moon JungSharma YaminiPereira MandyLee Young EunSo Eui YoungRoe Allyson ShermanSingh NavneetReginato Anthony MVentetuolo Corey EWilkins Martin RZhao LanRhodes Christopher JKlinger James RLiang Olin D