Inflammation Research最新文献

{"title":"Cellular crosstalk between endothelial and vascular smooth muscle cells via the BACH1/COL3A1 axis promotes vascular calcification in chronic kidney disease.","authors":"Jing Ning, Sitian Fang, Minzi Qiu, Honghong Zou, Yanxia Chen","doi":"10.1007/s00011-026-02339-x","DOIUrl":"10.1007/s00011-026-02339-x","url":null,"abstract":"<p><strong>Background: </strong>High phosphate levels lead to significant pathological changes in vascular smooth muscle cells (VSMCs) and endothelial cells, driving vascular disease in chronic kidney disease (CKD). Endothelial cell senescence plays a major role in this process, promoting vascular calcification by fostering a pro-inflammatory and pro-osteogenic environment. Interaction between VSMCs and endothelial cells further accelerates calcification, although the precise mechanisms remain incompletely understood.</p><p><strong>Methods: </strong>Exosomes were isolated and characterized, with RT-qPCR, western blot, immunohistochemistry (IHC), and immunofluorescence (IF) assays used to confirm gene and protein expression. Chromatin immunoprecipitation (ChIP) and dual-luciferase assays were conducted to assess interactions between BACH1 and COL3A1. A 5/6 nephrectomy-induced CKD mouse model was established, and Alizarin Red S staining, Von Kossa staining, calcium content measurement, and ALP activity assays were performed to assess vascular calcification and osteogenic differentiation.</p><p><strong>Results: </strong>Knocking down BACH1 reduced high phosphate-induced senescence in endothelial cells and suppressed TNF-α-induced EndMT in these cells. BACH1 also enhanced COL3A1 expression by activating its transcription. Endothelial cell-derived COL3A1 was associated with exosomes, and HAoEC-derived exosomes were internalized by VSMCs, thereby promoting calcification-related phenotypes in VSMCs. In vivo, systemic COL3A1 knockdown attenuated CKD-associated vascular calcification, EndMT-like changes, and senescence.</p><p><strong>Conclusion: </strong>In summary, BACH1 regulates COL3A1, facilitating communication between endothelial cells and VSMCs through exosomes, thereby promoting vascular calcification in CKD. These findings highlight that targeting the BACH1-COL3A1 axis and exosome-mediated endothelial-VSMC communication may represent a potential therapeutic strategy.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-dependent lysophosphatidic acid signalling in inflammation: evidence hierarchy, myeloid regulation and translational gaps.","authors":"Wataru Nagata, Kunio Takada","doi":"10.1007/s00011-026-02337-z","DOIUrl":"10.1007/s00011-026-02337-z","url":null,"abstract":"<p><strong>Background: </strong>Lysophosphatidic acid (LPA) has been extensively reviewed in receptor pharmacology, fibrosis, cancer, vascular biology and neural injury. Its role in inflammation remains difficult to interpret because well-replicated pathogenic or pro-remodelling actions coexist with selected macrophage-regulatory effects reported under defined experimental conditions.</p><p><strong>Findings: </strong>This structured narrative review provides an evidence-weighted framework for interpreting these divergent findings. The strongest evidence supports LPA as an injury- and remodelling-associated signal in vascular-stromal programmes, pain-associated settings and tumour immune escape. By contrast, LPA-mediated attenuation of selected LPS/TLR4-driven macrophage responses is biologically plausible but incompletely replicated and receptor-divergent. The more specific LPAR1-dependent model of M2-like and metabolic macrophage reprogramming remains less independently validated, especially in primary human myeloid cells and physiologically plausible concentration ranges.</p><p><strong>Conclusions: </strong>LPA should not be classified as simply pro-inflammatory or anti-inflammatory. Anti-inflammatory LPA models should be regarded as experimentally plausible but translationally unproven until validated using defined LPA species, receptor-resolved perturbation and concentration-resolved human myeloid-cell systems.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of gut bacterial extracellular vesicles on angiogenic potential and vascular integrity: positive and negative aspects.","authors":"Sara Aghakhani Chegeni, Banafsheh Yalameha, Somayyeh Rashidi, Gonja Javani, Narjes Seddighi, Hesam Saghaei Bagheri, Masoud Khalifezadeh, Golbarg Roozbahani, Sara Molaaghaee-Rouzbahani, Reza Rahbarghazi","doi":"10.1007/s00011-026-02334-2","DOIUrl":"10.1007/s00011-026-02334-2","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are intercellular mediators in prokaryotic and eukaryotic systems that have the potential to regulate various physiological and pathological processes in recipient cells. Among them, bacterial extracellular vesicles (BEVs), including Gram-negative outer membrane vesicles (OMVs) and Gram-positive membrane vesicles (MVs) produced by the gut microbiota, have special roles in humans and animals. Due to their nanoscale dimensions and distinct molecular payloads, BEVs can cross biological barriers, including the vascular endothelium, to reach distant target tissues and affect various pathophysiological processes. Dysbiosis and compromised epithelial barriers facilitate the systemic dissemination of gut microbiota-derived BEVs, increasing the risk of diseases such as atherosclerosis and cardiovascular disease. Importantly, while this review emphasizes symbiotic intestinal BEVs, evidence from oral and pathogenic bacteria has also been integrated as indirect mechanistic sources to shed more light on BEV-induced endothelial dysfunction and altered angiogenesis. Here, we aimed to highlight the impact of BEVs on the vascular compartment, focusing on endothelial cells (ECs) in terms of molecular and cellular events. Understanding the underlying mechanisms will enable us to develop sophisticated engineered BEVs to control and inhibit certain pathological conditions.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV4/IP3R-1-mediated endothelial pyroptosis drives pulmonary microvascular endothelial permeability in endotoxin-induced acute lung injury.","authors":"Shasha Liu, Shuan Dong, Lirong Gong, Jing Yang, Huayang Liu, Meiling Piao, Ya Wu, Huirong An, Li Zhang, Jianbo Yu","doi":"10.1007/s00011-026-02327-1","DOIUrl":"10.1007/s00011-026-02327-1","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute lung injury (ALI) is characterized by edema resulting from increased vascular permeability. Transient receptor potential vanilloid 4 (TRPV4) interacts with inositol 1,4,5-trisphosphate receptor type 1 (IP3R-1) through calmodulin-binding domains and regulates vascular permeability. However, the specific mechanisms underlying the roles of TRPV4 and IP3R-1 in endothelial pyroptosis and vascular permeability remain unclear.</p><p><strong>Methods: </strong>EMPs were measured in septic patients and controls, and co-cultured with human pulmonary microvascular endothelial cells (HPMECs). LPS-induced ALI was assessed in wild-type or Gsdmd^-/- mice with pharmacological modulation of TRPV4, as well as in Trpv4^-/- mice. Pyroptosis was detected in IP3R-1-silenced HPMECs treated with LPS and TRPV4 agonist. IP3R-1/GSDMD interaction was confirmed by structural prediction, Co-IP, and immunofluorescence. Intracellular Ca²⁺ was detected by flow cytometry, and tissue Ca²⁺ was visualized by in vivo imaging.</p><p><strong>Results: </strong>Elevated EMPs in septic patients enhanced endothelial permeability, upregulated TRPV4 and GSDMD-NT generation in HPMECs. TRPV4 promotes HPMECs permeability and pyroptosis in an IP3R-1-dependent manner. TRPV4 inhibition attenuated lung injury and ameliorated pulmonary dysfunction, while Trpv4 knockdown improved survival. Knockdown of IP3R-1 reduced intracellular Ca²⁺ and mtDNA levels in HPMECs. In vivo imaging revealed attenuated Ca²⁺ accumulation in Trpv4^-/- mice. The interaction between TRPV4/IP3R-1 and GSDMD was Ca²⁺-dependent.</p><p><strong>Conclusions: </strong>TRPV4 disrupts HPMEC integrity via IP3R-1 and triggers GSDMD-mediated pyroptosis through a Ca²⁺-dependent mechanism, exacerbating LPS-induced ALI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKR⁺CD8⁺ T cells and iNKT cells protect mice from AOM/DSS-induced colorectal cancer under conditions of IFNγ-mediated hyperinflammation.","authors":"Hyun Jung Park, Sung Won Lee, Yun Hoo Park, Tae-Cheol Kim, Luc Van Kaer, Seokmann Hong","doi":"10.1007/s00011-026-02325-3","DOIUrl":"10.1007/s00011-026-02325-3","url":null,"abstract":"<p><strong>Background: </strong>Interferon-gamma (IFNγ) is a pivotal cytokine in immune surveillance and inflammation, yet its precise role in colorectal cancer (CRC) remains controversial due to its dual involvement in tumor suppression and immune evasion. Although natural killer cell receptor (NKR)⁺CD8⁺ T cells and invariant natural killer T (iNKT) cells contribute to anti-tumor immunity, how these cells regulate CRC progression under IFNγ-mediated, inflammatory conditions remains unclear.</p><p><strong>Methods: </strong>An azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC model was established in heterozygous Yeti mice with IFNγ-mediated hyperinflammation. Using flow cytometry and histology, we evaluated tumor burden, histopathology, and immune cell infiltration in tumor tissues. NKR⁺CD8⁺ T cells were induced by IL15 treatment, and their anti-tumor efficacy was validated by adoptive transfer. The functional contribution of iNKT cells was assessed using iNKT cell-deficient Yeti/Jα18 knockout (KO) mice. Clinical relevance was determined by analyzing public transcriptomic datasets from non-metastatic and metastatic CRC patients using gene set enrichment (GSE) and protein interaction network (STRING) analyses.</p><p><strong>Results: </strong>We found that Yeti mice display significantly blunted CRC development compared to wild-type (WT) controls. Furthermore, these IFNγ-mediated anti-tumor immune responses were attributed to increased tumor infiltration by CD8⁺ T cells expressing NKRs. Adoptive transfer experiments demonstrated that NKR⁺CD8⁺ T cells are potent anti-tumor effectors. Tumor-infiltrating iNKT cells in Yeti mice exhibited enhanced IFNγ and reduced IL10 production. Yeti mice lacking iNKT cells exhibited reduced tumor infiltration by NKR⁺CD8⁺ T cells, indicating that iNKT cells, particularly those producing IFNγ, are critical for controlling CRC development. Through GSE and STRING analyses, we found that non-metastatic patients exhibited increased IFNγ responses, reflected by greater enrichment of IFNγ-related gene ontology categories, compared with metastatic patients.</p><p><strong>Conclusions: </strong>NKR⁺CD8⁺ T cells in Yeti mice with elevated IFNγ levels suppress CRC development in an iNKT cell-dependent manner, suggesting that NKR⁺CD8⁺ T cells and iNKT cells cooperate to drive optimal anti-tumor immune responses against CRC during IFNγ hyperinflammation. Our findings highlight a potential immunotherapeutic strategy for CRC by reinforcing IFNγ-dependent anti-tumor responses.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MICA gene modulates immune microenvironment and comorbid mechanisms in diffuse large B-cell lymphoma and primary Sjögren's syndrome.","authors":"Hancheng Qin, Kuai Yu, Xuefei Deng, Tiantian Sun, Yaqun Wang, Mei Xie, Xiaojun Xu, Yunxin Zeng, Wei Xiao","doi":"10.1007/s00011-026-02263-0","DOIUrl":"10.1007/s00011-026-02263-0","url":null,"abstract":"<p><strong>Objective: </strong>To identify shared molecular mechanisms and crosstalk genes (CGs) between diffuse large B-cell lymphoma (DLBCL) and primary Sjögren's syndrome (PSS), and to explore the role of MICA in the immune microenvironment (IME).</p><p><strong>Methods: </strong>Bioinformatics analysis of GEO datasets identified differentially expressed genes (DEGs). Enrichment, immune infiltration, and Mendelian randomization analyses were performed. Diagnostic biomarkers were screened using Lasso regression. Functional roles of MICA were validated in SUDHL-6 cells via overexpression/knockdown, assessing immune cell infiltration, cytokine secretion, proliferation, and apoptosis.</p><p><strong>Results: </strong>We identified 50 shared DEGs. RPL31, HNMT, and IFI27 were defined as diagnostic biomarkers. MR analysis confirmed a causal effect of PSS on DLBCL risk. MICA interacted with RPL31 and HNMT. MICA overexpression enhanced CD8⁺ T-cell infiltration and activation, elevated pro-inflammatory cytokine release, suppressed tumor cell proliferation, and promoted apoptosis. Conversely, MICA knockdown suppressed anti-tumor immune activity and promoted tumor growth.</p><p><strong>Conclusion: </strong>MICA plays a key role in shaping the immune microenvironment of DLBCL and PSS. By reinforcing anti-tumor immune responses and limiting tumor growth, it emerges as a promising biomarker and therapeutic target in both diseases.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Tph cell differentiation via farnesoid X receptor of dendritic cells in inflammatory bowel disease.","authors":"Zhen Hu, Minya Liu, Chengkai Zhu, Na Li, Xiaotian Chen, Binlin Da, Yi Li, Chenggong Yu","doi":"10.1007/s00011-026-02332-4","DOIUrl":"10.1007/s00011-026-02332-4","url":null,"abstract":"<p><strong>Background: </strong>Peripheral helper T cells represent a recently characterized subset of CD4⁺ T cells present in inflammatory bowel disease (IBD) patients. Bile acids act as signaling molecules in immune regulation. However, the role of bile acids in Tph cell differentiation remains unclear.</p><p><strong>Methods: </strong>Immunofluorescence staining was used to detect the presence of Tph cells in intestinal tissue samples; Wild-type (WT) and Fxr^-/- mice were treated with or without the FXR agonist obeticholic acid (OCA) in dextran sulfate sodium (DSS)-induced acute colitis. The proportions of Tph cells and innate immune cells were analyzed by FACS. Bone marrow-derived dendritic cells (BMDCs) and naïve T cells of WT and Fxr^-/- mice were sorted, differentiated and cultured in vitro to observe the regulatory effects of FXR on BMDCs function and Tph cell differentiation.</p><p><strong>Results: </strong>Tph proportion was significantly elevated in inflamed intestinal tissues. OCA treatment increased the Tph cell proportion in the intestinal LP of WT mice. The proportion of dendritic cells (DCs) in the LP of Fxr^-/- mice was significantly lower than WT mice after DSS-mediated colitis induction. FXR deficiency impaired the ability of BMDCs to induce Tph cell differentiation in vitro. CD11c and MHC-II expression levels were reduced in BMDCs from Fxr^-/- mice upon stimulation with LPS. FXR deficiency activated the PPAR-γ signaling pathway and decreased IL-12 expression in BMDCs.</p><p><strong>Conclusion: </strong>Tph cell levels were elevated in inflamed intestinal tissues. FXR suppression in BMDCs was associated with activated PPAR-γ signaling; and with reduced DC maturation, IL-12 secretion, and Tph cell differentiation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International comparison of neutrophil surface markers after severe trauma is feasible using point of care flowcytometry - results from a pilot study.","authors":"Christian Thomas Hübner, Emma de Fraiture, Nathalie Piaz, Louise Virginie Duebel, Roman Pfeifer, Sanne Brands, Felix Karl-Ludwig Klingebiel, Yannik Kalbas, Paolo Cinelli, Leo Koenderman, Falco Hietbrink, Hans-Christoph Pape, Michel Paul Johan Teuben","doi":"10.1007/s00011-026-02335-1","DOIUrl":"10.1007/s00011-026-02335-1","url":null,"abstract":"<p><strong>Introduction: </strong>The dynamics of cell surface marker expression on systemic neutrophils provide valuable insights into the post-traumatic immune response. Recent advances in point-of-care (PoC) technologies allow for rapid on-site neutrophil analysis. The current study aimed to proof, if results of PoC measurements are comparable between two study centers.</p><p><strong>Methods: </strong>A well-established laboratory protocol for fully automated PoC flowcytometry analysis of neutrophils was applied inside the trauma bay of two level 1 trauma centers. We analyzed the neutrophil surface patterns CD16, CD11b, CD62L, CD10 and CD64 and compared the results between two centers both in heathy controls and patients.</p><p><strong>Results: </strong>28 Polytrauma patients were included. The measurements at both centers revealed similar results with respect to the expression neutrophil activation markers in patients with different trauma severities. Particularly the expression of CD16, CD11b and CD10 were very comparable between both centers in both healthy controls and trauma patients.</p><p><strong>Conclusion: </strong>This study demonstrates the successful implementation of a fully automated PoC neutrophil analysis infrastructure from one trauma center to another facilitating multicenter flow cytometry studies. This paves the way for advanced immune monitoring that could significantly improve personalized clinical decision-making.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.","authors":"Mohamed Alsabbagh, Satanay Z Hubrack, Lara Gamgoum, Maryiam J A Osman, Katherine E Ford, Alya Al Shakaki, Amal Robay, Housam Sarakbi, Samar Al Emadi, Rafah Mackeh, Khalid A Fakhro, Bernice Lo","doi":"10.1007/s00011-026-02326-2","DOIUrl":"10.1007/s00011-026-02326-2","url":null,"abstract":"<p><strong>Background: </strong>A20 is an anti-inflammatory protein that suppresses nuclear factor-κB (NF-κB)-mediated inflammatory gene expression and inhibits cell death. Disruption of A20 function results in defective suppression of the NF-κB pathway, manifesting in diverse autoimmune and autoinflammatory conditions. While autosomal dominant A20 mutations have been identified to cause autoinflammatory disease, recessive A20 mutations causing disease have not been previously described.</p><p><strong>Methods: </strong>We utilized whole exome sequencing to identify the variant of interest. In silico structural modeling as well as immunoprecipitation were used to ascertain A20's interaction with linear ubiquitin, coupled with flow cytometric analysis and western blotting to measure the expression of NF-κB activation markers. We quantified NF-κB pathway activity using NF-κB reporter assay.</p><p><strong>Results: </strong>Here, we report a novel homozygous mutation in the A20 protein responsible for early-onset lupus-like disease starting at four years of age. We show that the A20 E781K variant, situated in the seventh zinc finger domain of A20, compromises the protein's ability to bind linear ubiquitin, resulting in a functional hypomorph with a reduced capacity to inhibit NF-κB activation and downstream gene expression in HEK293 cells.</p><p><strong>Conclusion: </strong>Our findings characterize a critical mutation associated with early-onset lupus-like disease in its recessive form and continue to highlight the important role of A20 in maintaining immune homeostasis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.","authors":"Nan Gao, Song Yang, Wei-Jian Zhang, Hao-Tian Lu, Zheng-Nan Zhang, Yi-Xin Qian, Guo-Qiang Zhang","doi":"10.1007/s00011-026-02310-w","DOIUrl":"10.1007/s00011-026-02310-w","url":null,"abstract":"<p><strong>Objective and design: </strong>This narrative review synthesizes current evidence on the role of SERPINE1/PAI-1 in acute respiratory distress syndrome (ARDS), with particular emphasis on inflammation-coagulation-fibrinolysis crosstalk.</p><p><strong>Material or subjects: </strong>Published experimental, translational, genetic, and clinical studies addressing SERPINE1/PAI-1 in ARDS and related critical illnesses were summarized.</p><p><strong>Treatment: </strong>Not applicable.</p><p><strong>Methods: </strong>We summarized evidence on the pathobiological functions, cellular sources, biomarker potential, genetic associations, and therapeutic implications of SERPINE1/PAI-1.</p><p><strong>Results: </strong>SERPINE1 limits tissue-type and urokinase-type plasminogen activator activity, thereby promoting hypofibrinolysis and persistent fibrin deposition in the injured lung. Experimental and clinical evidence further links elevated PAI-1 to inflammatory amplification, endothelial injury, pulmonary microvascular thrombosis, greater disease severity, and adverse outcomes, although the strength of evidence and the degree of causal support vary across these processes. High-expression SERPINE1 variants may also influence clinical outcomes in selected critical illness settings. Pharmacological PAI-1 inhibition is biologically plausible, but its translation to ARDS remains limited by disease heterogeneity, uncertainty regarding treatment timing, and the risk of bleeding.</p><p><strong>Conclusions: </strong>SERPINE1 is a potentially important integrative regulator and biomarker of dysregulated inflammation, coagulation, and fibrinolysis in ARDS. Future studies should clarify its causal, cell-specific, and phenotype-dependent roles to facilitate the development of targeted therapeutic strategies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}