Respiratory Research最新文献

{"title":"Correction: Complement activity and autophagy are dysregulated in the lungs of patients with nonresolvable COVID‑19 requiring lung transplantation.","authors":"Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N LeFebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana","doi":"10.1186/s12931-025-03258-x","DOIUrl":"10.1186/s12931-025-03258-x","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"198"},"PeriodicalIF":5.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First nomogram for predicting interstitial lung disease and pulmonary arterial hypertension in SLE: a machine learning approach.","authors":"Qian Niu, Qian Li, Shuaijun Chen, Lingyan Xiao, Jing Luo, Meng Wang, Linjie Song","doi":"10.1186/s12931-025-03273-y","DOIUrl":"10.1186/s12931-025-03273-y","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are severe, life-threatening complications of systemic lupus erythematosus (SLE). Early identification of high-risk patients remains challenging due to the lack of validated predictive tools. We aimed to develop and validate the first machine learning-based nomogram integrating routine clinical indicators to predict SLE-ILD-PAH risk.</p><p><strong>Methods: </strong>Using a retrospective cohort design, we analyzed 338 SLE patients (2007-2019), including 193 with ILD-PAH and 145 controls. Univariable and multivariable logistic regression identified independent predictors, followed by nomogram construction and random forest modeling. Model performance was assessed via calibration curves and decision curve analysis (DCA).</p><p><strong>Results: </strong>Age, C-reactive protein (CRP), anti-dsDNA, pericarditis, and SLE Disease Activity Index (SLEDAI) were independently associated with the prevalence of ILD-PAH in SLE patients. The 5 variables were selected to construct the nomogram model. Calibration curves and decision curve analysis indicated the clinical utility of the nomogram. Receiver operating characteristics (ROC) curves analysis demonstrated excellent discrimination (AUC = 0.871, 95% CI: 0.833-0.910). Forest plot analysis further confirmed the diagnostic weight of each variable.</p><p><strong>Conclusions: </strong>We developed the first nomogram incorporating age, CRP, anti-dsDNA, pericarditis, and SLEDAI to predict SLE-ILD-PAH risk. This machine learning-enhanced tool leverages routine clinical data, enabling early risk stratification and personalized monitoring. Future studies should validate its utility in guiding therapies and improving outcomes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"197"},"PeriodicalIF":5.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenylacetylglutamine produced from injury lung alveolar epithelial cells promotes the function of BMSCs by regulating NONRATT006276.2/Mapt pathway.","authors":"Tianyun Yang, Juan Peng, Rongrong Ren, Lin Song","doi":"10.1186/s12931-025-03261-2","DOIUrl":"10.1186/s12931-025-03261-2","url":null,"abstract":"<p><p>Mesenchymal stem cell (MSC)-based therapy regenerates damaged structures of the respiratory system and restores lung function, thus providing a promising therapeutic approach for chronic obstructive pulmonary disease. Understanding the communication between injured alveolar cells and MSCs can improve the efficiency of MSC-based therapies. The present study analyzed the untargeted metabolomics of the supernatant of AEC-II injury induced by cigarette smoke extract and identified 205 differential metabolites. Phenotypic assays indicated that phenylacetylglutamine (PAG) significantly promoted the migration and mitochondrial function of bone marrow MSCs (BMSCs). Whole-transcriptome sequencing (WT-seq) was used to analyze the long noncoding RNA (lncRNA) and mRNA expression profiles of BMSCs treated with PAG. The upregulated lncNRA NONRATT006276.2 (NRT6276.2) and its trans-regulated gene, microtubule-associated protein tau (Mapt), were identified based on the lncRNA-mRNA co-expression network and bioinformatics analysis. The knockdown of NRT6276.2 or Mapt inhibited the positive effects of PAG on BMSCs. Furthermore, Mapt overexpression reversed the phenotype of BMSCs inhibited by silencing NRT6276.2. In conclusion, PAG enhanced the migration and mitochondrial function of BMSCs by regulating the NRT6276.2/Mapt pathway. This study clarified the positive effects of PAG produced by injured lung cells on transplanted MSCs, providing a potential new strategy to enhance the efficiency of MSC-based therapies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"196"},"PeriodicalIF":5.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of quantitative CT chest imaging to derive and assess a radiographic phenotype of deployment-related constrictive bronchiolitis.","authors":"Alexander J Bell, Maria Masotti, Sundaresh Ram, Gregory Pappas, Robert F Miller, Ella A Kazerooni, Charles R Hatt, MeiLan K Han, Bradley W Richmond, Michael J Falvo, Craig J Galban, John J Osterholzer","doi":"10.1186/s12931-025-03269-8","DOIUrl":"10.1186/s12931-025-03269-8","url":null,"abstract":"<p><strong>Background: </strong>Efforts to phenotype veterans that developed respiratory symptoms following deployments to the Southwest Asia Theater of Military Operation have been limited by the insensitivity of current non-invasive testing to objectively identify deployment-related constrictive bronchiolitis and other features of chronic lung injury. In this study, we derived a quantitative CT (QCT)-based radiographic phenotype of biopsy-proven deployment-related constrictive bronchiolitis (DRCB) and assessed its ability to assist in the phenotyping of non-biopsied formerly deployed symptomatic veterans.</p><p><strong>Methods: </strong>QCT analysis combined with demographic, physiologic, symptom, and exposure data was obtained from three cohorts: military personnel with biopsy-proven deployment-related constrictive bronchiolitis (DRCB, n = 37), formerly deployed symptomatic veterans (FDSV, n = 71), and asymptomatic civilians (Control, n = 98). Differences in unadjusted QCT metrics and demographic variables between cohorts were identified and further assessed by principal component analysis. Thereafter, adjusted data from the DRCB cohort was used to derive a QCT-based radiographic phenotype of DRCB expressed as a DRCB-Probability Index (DRCB-PI). Application of the DRCB-PI to the FDSV cohort was used to assess additional phenotypic metrics associated with the DRCB phenotype (DRCB-PI > 0.5).</p><p><strong>Results: </strong>Individual unadjusted QCT metrics for functional small airways disease and high attenuation area were elevated in DRCB and FDSV cohorts (relative to Control). Primary component analysis revealed that DRCB and FDSV cohorts overlapped and were distinguished from the Control cohort. The FDSV subjects whose DRCB-PI was > 0.5 had greater evidence of small airways disease (assessed by oscillometry and QCT) and self-reported more intense immediate health effects to their exposures to military burn pit smoke, and sand and dust.</p><p><strong>Conclusions: </strong>Application of a QCT-derived radiographic phenotype of DRCB identified a subset of veterans with evidence of abnormal small airways and more severe self-reported health effects following inhalational exposures during military deployment. Future studies incorporating QCT may help establish non-invasive strategies to detect DRCB and other forms of chronic lung injury.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"195"},"PeriodicalIF":5.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.","authors":"Na Li, Wenyue Zhao, Jiale Li, Dengfeng Zhang, Kejun Li, Mengmeng Yang, Xinran Lu, Liqing Du, Chang Xu, Qiang Liu","doi":"10.1186/s12931-025-03271-0","DOIUrl":"10.1186/s12931-025-03271-0","url":null,"abstract":"<p><strong>Objective: </strong>Dysregulated autophagy plays a critical role in the pathogenesis of pulmonary fibrosis. The stress protein TRIB3 has been correlated with abnormal autophagy, but its specific contribution to radiation-induced pulmonary fibrosis (RIPF) remains unclear. This study aimed to elucidate the role of TRIB3 in RIPF progression.</p><p><strong>Methods: </strong>We conducted RNA-sequencing of rat RIPF lung tissue to analyze the transcriptomic profile and determine gene expression changes in murine with RIPF. We established mouse models with alveolar epithelial type II cells (AEC II)-specific knockdown or overexpression of TRIB3 to elucidate its role in RIPF progression. We utilized mRFP-GFP-LC3 fluorescent reporter cells, nanoparticle tracking analysis, immunofluorescence and immunoprecipitation assays to uncover the underlying mechanisms.</p><p><strong>Results: </strong>TRIB3 expression was elevated in irradiated AEC II. Silencing TRIB3 in AEC II mitigated RIPF in mice, whereas its overexpression exacerbated the condition. Mechanistically, TRIB3 interacted with the LC3-interacting region (LIR) motif and ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1), an autophagic receptor protein, thereby inhibiting autophagic flux in AEC II cell line MLE12. This inhibition increased exosome secretion and facilitated crosstalk between MLE12 cells and fibroblasts, ultimately enhancing the proliferation and extracellular matrix production of lung fibroblasts.</p><p><strong>Conclusion: </strong>TRIB3 in AEC II inhibits autophagic flux by interacting with SQSTM1, thereby increasing exosome secretion, which promotes fibroblast proliferation and extracellular matrix production, contributing to RIPF progression.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"194"},"PeriodicalIF":5.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung lipids associated with smoking and ECIG use in a cross-sectional study and clinical trial.","authors":"Joseph P McElroy, Min-Ae Song, John R Barr, Michael S Gardner, Garret Kinnebrew, Zsuzsanna Kuklenyik, Jennifer D Kusovschi, Jon C Rees, Benjamin C Blount, MuChun Tsai, Mark D Wewers, Sahar Kamel, Sarah A Reisinger, Amarnath Singh, Daniel Y Weng, Peter G Shields","doi":"10.1186/s12931-025-03267-w","DOIUrl":"10.1186/s12931-025-03267-w","url":null,"abstract":"<p><strong>Background: </strong>While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis.</p><p><strong>Methods: </strong>Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively.</p><p><strong>Results: </strong>In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial.</p><p><strong>Conclusions: </strong>Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease.</p><p><strong>Trial registration: </strong>The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"193"},"PeriodicalIF":5.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of early idiopathic pulmonary fibrosis: current status and future perspective.","authors":"Xinya Wang, Xinrui Xia, Yihan Hou, Huaizhe Zhang, Wenyang Han, Jianqi Sun, Feng Li","doi":"10.1186/s12931-025-03270-1","DOIUrl":"10.1186/s12931-025-03270-1","url":null,"abstract":"<p><p>The standard approach to diagnosing idiopathic pulmonary fibrosis (IPF) includes identifying the usual interstitial pneumonia (UIP) pattern via high resolution computed tomography (HRCT) or lung biopsy and excluding known causes of interstitial lung disease (ILD). However, limitations of manual interpretation of lung imaging, along with other reasons such as lack of relevant knowledge and non-specific symptoms have hindered the timely diagnosis of IPF. This review proposes the definition of early IPF, emphasizes the diagnostic urgency of early IPF, and highlights current diagnostic strategies and future prospects for early IPF. The integration of artificial intelligence (AI), specifically machine learning (ML) and deep learning (DL), is revolutionizing the diagnostic procedure of early IPF by standardizing and accelerating the interpretation of thoracic images. Innovative bronchoscopic techniques such as transbronchial lung cryobiopsy (TBLC), genomic classifier, and endobronchial optical coherence tomography (EB-OCT) provide less invasive diagnostic alternatives. In addition, chest auscultation, serum biomarkers, and susceptibility genes are pivotal for the indication of early diagnosis. Ongoing research is essential for refining diagnostic methods and treatment strategies for early IPF.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"192"},"PeriodicalIF":5.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription factor ZNF266 suppresses cancer progression by modulating CA9-mediated intracellular pH alteration in lung adenocarcinoma.","authors":"Shencheng Ren, Junkan Zhu, Guangyao Shan, Jiaqi Liang, Yunyi Bian, Han Lin, Haochun Shi, Binyang Pan, Guangyin Zhao, Huiqin Yang, Xiaolong Huang, Cheng Zhan, Di Ge, Guoshu Bi","doi":"10.1186/s12931-025-03278-7","DOIUrl":"10.1186/s12931-025-03278-7","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the leading cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Despite extensive research efforts, the role of transcription factors in LUAD progression remains largely uncharacterized. In this study, we focused on ZNF266, a transcription factor whose impacts on LUAD have not been investigated.</p><p><strong>Methods: </strong>Using high-throughput sequencing data, we observed a significant downregulation of ZNF266 expression in LUAD tissues. To validate this finding, we conducted a retrospective analysis of nearly three thousand LUAD patients' data from public databases and our institution. Functional studies were performed using cell lines, organoids, and xenograft models to assess the role of ZNF266 in LUAD progression. RNA sequencing, chromatin immunoprecipitation, DNA pull-down assays, and dual-luciferase reporter assays were employed to elucidate the underlying mechanism. Additionally, adeno-associated virus (AAV)-mediated overexpression of ZNF266 was used to evaluate its therapeutic potential.</p><p><strong>Results: </strong>Patients with low ZNF266 expression had poorer prognosis compared to those with high expression. ZNF266 inhibits the malignant phenotypes of LUAD, including proliferation, migration, and invasion. Mechanistically, ZNF266 binds to the promoter region of CA9, suppressing its transcription. This leads to a reduction in intracellular pH and subsequent inhibition of the mTOR signaling pathway, which is crucial for cancer cell growth and survival. Furthermore, AAV-mediated overexpression of ZNF266 significantly inhibited tumor growth in patient-derived xenograft models.</p><p><strong>Conclusions: </strong>Our study demonstrated that ZNF266 inhibits LUAD progression in a pH-dependent manner via modulating CA9 expression, uncovering its therapeutic significance for LUAD treatment.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"191"},"PeriodicalIF":5.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding mechanisms and protein markers in lung-brain axis.","authors":"Shiqian Huang, Yuxi Zhou, Haipeng Ji, Tianhao Zhang, Shiya Liu, Lulin Ma, Daling Deng, Yuanyuan Ding, Linlin Han, Shaofang Shu, Yu Wang, Xiangdong Chen","doi":"10.1186/s12931-025-03272-z","DOIUrl":"10.1186/s12931-025-03272-z","url":null,"abstract":"<p><strong>Background: </strong>The lung-brain axis represents a complex bidirectional communication network that is pivotal in the crosstalk between respiratory and neurological functions. This review summarizes the current understanding of the mechanisms and protein markers that mediate the effects of lung diseases on brain health.</p><p><strong>Main findings: </strong>In this review, we explore the mechanisms linking lung injury to neurocognitive impairments, focusing on neural pathways, immune regulation and inflammatory responses, microorganism pathways, and hypoxemia. Specifically, we highlight the role of the vagus nerve in modulating the central nervous system response to pulmonary stimuli; Additionally, the regulatory function of the immune system is underscored, with evidence suggesting that lung-derived immune mediators can traverse the blood-brain barrier, induce neuroinflammation and cognitive decline; Furthermore, we discuss the potential of lung microbiota to influence brain diseases through microbial translocation and immune activation; Finally, the impact of hypoxemia is examined, with findings indicating that it can exacerbate cerebral injury via oxidative stress and impaired perfusion. Moreover, we analyze how pulmonary conditions, such as pneumonia, ALI/ARDS, and asthma, contribute to neurological dysfunction. Prolonged mechanical ventilation can also contribute to cognitive impairment. Conversely, brain diseases (e.g., stroke, traumatic brain injury) can lead to acute respiratory complications. In addition, protein markers such as TLR4, ACE2, A-SAA, HMGB1, and TREM2 are crucial to the lung-brain axis and correlate with disease severity. We also discuss emerging therapeutic strategies targeting this axis, including immunomodulation and microbiome engineering. Overall, understanding the lung-brain interplay is crucial for developing integrated treatment strategies and improving patient outcomes. Further research is needed to elucidate the molecular mechanisms and foster interdisciplinary collaboration.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"190"},"PeriodicalIF":5.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geranylgeranyl diphosphate synthase deficiency impairs efferocytosis and resolution of acute lung injury.","authors":"Jiajia Jin, Lihong Ma, Lulu Li, Xinyu Zhou, Suhua Zhu, Kaikai Shen, Qiuli Xu, Bei Jiang, Yanli Gu, Qianshan Ding, Hong Qian, Tangfeng Lv, Yong Song","doi":"10.1186/s12931-025-03241-6","DOIUrl":"10.1186/s12931-025-03241-6","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) are major causes of mortality of critically ill patients. Impaired macrophage-mediated clearance of apoptotic cells (efferocytosis) in ARDS contributes to prolonged inflammation, yet the underlying mechanisms remain unclear. In this study, we investigated the role of geranylgeranyl diphosphate synthase (GGPPS) in efferocytosis during lung injury resolution. We identified dynamic changes in GGPPS expression in lung macrophages and circulating monocytes throughout the progression and resolution phases of acute lung injury (ALI). Myeloid-specific GGPPS knockout mice exhibited prolonged lung inflammation, increased accumulation of apoptotic neutrophils, a higher number of recruited macrophages, and a reduced number of resident macrophages. Notably, recruited macrophages play a dominant role in efferocytosis compared to resident macrophages. GGPPS deficiency suppressed efferocytosis in both macrophage subsets in vivo and in vitro. Mechanistically, GGPPS knockout disrupted AXL signaling in recruited macrophages. Importantly, administration of geranylgeraniol (GGOH) rescued the delayed resolution of lung injury, restored efferocytosis, and increased the suppressed AXL expression in CKO mice. Collectively, this study identifies GGPPS as a key regulator of AXL-mediated efferocytosis in recruited macrophages, highlighting its potential as a therapeutic target to accelerate ARDS resolution.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"189"},"PeriodicalIF":5.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}