Ask about this productRelated genes to: PAI1 protein
- Gene:
- SERPINE1 NIH gene
- Name:
- serpin family E member 1
- Previous symbol:
- PLANH1, PAI1
- Synonyms:
- PAI
- Chromosome:
- 7q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-04-23
Related products to: PAI1 protein
Related articles to: PAI1 protein
- 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 - Smooth muscle cells (SMCs) comprise the majority of cells in human atherosclerotic lesions and are thought to be a major source of cholesterol-overloaded foam cells in human and mouse atheromas. However, the transcriptomic profile, specific markers, and biologic itinerary of SMC foam cells relative to macrophage foam cells remain poorly defined. - Source: PubMed
Publication date: 2026/06/01
Allahverdian SimaMao YuanchengXiang PinhaoBlanchard ValentinBölük AydinHart Patrick ACheng PaulLi Daniel YWorssam Matthew DArasu Uma ThanigaiTaipale MariKiema MiikaLaakkonen Johanna PÖrd TiitKaikkonen Minna UMiller Clint LQuertermous ThomasChan TeddyFrancis Gordon A - Vasculogenic mimicry (VM) refers to the capacity of cancer cells from aggressive tumors to form a set of sinuses and channels that mimic normal blood vessels and lack endothelial cells. The rapid growth of a tumor leads to a deficiency in normal vessels, followed by poor oxygen and nutrient supply to tumor cells and VM induction. Understanding the mechanisms behind the development of the VM phenotype is important for the development of new anti-cancer therapies. Previous reports indicate that, during VM formation by melanoma Mel Z cells, about 2000 developmental genes undergo dramatic changes in expression. To identify genes more tightly linked to VM development, we compared the transcriptomes of Mel Z and MDA-MB-231 cells (triple-negative breast cancer cells), which also form VM. Most of the genes that change expression differ substantially between these two cell types. However, we identified 51 up- and 98 downregulated genes common to both cell lines. The non-overlapping groups of these genes are involved in regulating cell adhesion and proliferation. The group of common upregulated genes includes nine genes controlling blood vessel development and tube morphogenesis. Two genes in this group ( and ) rapidly form numerous contacts with nucleoli during VM phenotype formation. We observed that knockdown of the gene prevents the development of VM in Mel Z cells. Our data indicate that the formation of VM by aggressive cancer cells might be controlled by a special set of genes. - Source: PubMed
Publication date: 2026/05/29
Tchurikov Nickolai AKlushevskaya Elena SLukicheva Viktoriya NKretova Antonina NChechetkin Vladimir RKravatskaya Galina IVartanian Amalia AAlembekov Ildar RKravatsky Yuri V - Sepsis is a life-threatening condition marked by excessive inflammation and immune dysregulation. Macrophages are central to this process. Podoplanin (PDPN), a transmembrane glycoprotein, is upregulated in inflammatory macrophages, but its role in sepsis remains unclear. - Source: PubMed
Publication date: 2026/06/08
Wang HongbinHeng JunfengZhang YuhongCui JieLi YanyanYu SunGu XiaoleiLu ShiqiZhao Yiming - Bone is a common site of breast cancer metastasis, which dramatically increases fracture risk. Recent bone metastasis studies show that mechanical loading is osteoprotective; however, little is known about how loading regulates breast cancer cell function in the unique bone mechanical environment, especially in combination with radiotherapy, one of the first-line treatments for advanced breast cancer patients. Here, we characterize the breast cancer cell response to a range of bone-mimicking fluid shears and determine how irradiation further modulates one candidate gene: . We found that irradiation, regardless of dosage, modulates expression and is sensitive to the timing of administration. Additionally, protein expression of accompanies a protumorigenic gene expression profile, which is elevated with higher-magnitude fluid shear stresses in a bone-mimicking 3D environment. Thus, we postulate that plasminogen activator inhibitor-1 (PAI-1) (encoded by ) is a critical growth factor contributing to osteolytic lesion development in the bone metastatic vicious cycle of breast cancer. - Source: PubMed
Publication date: 2026/06/11
Venkatesh ShreyaOrdonez AndreaThompson William RChuong Edward BLynch Maureen E