Frontiers in Cell and Developmental Biology最新文献

{"title":"Weibel-Palade bodies - secretory organelles at the interface of inflammation and hemostasis.","authors":"Julian Terglane, Volker Gerke","doi":"10.3389/fcell.2025.1624487","DOIUrl":"10.3389/fcell.2025.1624487","url":null,"abstract":"<p><p>Weibel-Palade bodies (WPB) are lysosome-related, secretory organelles unique to vascular endothelial cells. They serve as storage organelles for the pro-thrombotic and hemostatic glycoprotein von-Willebrand factor (VWF) as well as numerous other proteins involved in regulating local inflammatory responses and coagulation processes. WPB undergo a complex formation and maturation process mainly dictated by the post-translational maturation of VWF itself. They are born at the trans-Golgi network and then move on microtubules to the cell periphery where they are anchored at the actin cortex to await signals triggering their evoked exocytosis. During this process, VWF undergoes significant compaction that results in an elongated, cigar-like shape of the organelle. WPB also receive material from the endosomal system although the trafficking routes involved here have not been fully unveiled. Exocytosis of WPB is induced by various agonists signaling through intracellular Ca²⁺ or cAMP elevation. It requires mobilization of WPB from the actin cortex and involves a number of docking and fusion mediating protein assemblies. The evoked release of WPB contents converts the endothelial cell surface from a repellant one which permits unrestricted blood flow to an adhesive structure capable of interacting with circulating leukocytes and platelets. Thereby, the endothelium can initiate inflammatory processes and hemostasis when vessel injury has occurred. This review discusses recent developments in the maturation and exocytosis of WPB, focusing on the ionic milieu required for tight VWF packing, endosome-to-WPB transport of WPB cargo, and WPB exocytosis and cargo release.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1624487"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: insights into the interplay of molecular mechanisms and hypomorphicity.","authors":"Fadia Abu-Sailik, Nesrin Gariballa, Bassam R Ali","doi":"10.3389/fcell.2025.1580274","DOIUrl":"10.3389/fcell.2025.1580274","url":null,"abstract":"<p><p>Several autosomal-dominant monogenic disorders have been conclusively associated with mutations in TGFBR1 and TGFBR2, key receptors of the Transforming Growth Factor-β (TGFβ) signaling pathway. Although these disorders share a common cardiovascular connective tissue manifestation, different mutations present with strikingly distinctive clinical presentations leading to distinct disorders, including Loeys-Dietz syndrome Marfan syndrome type 2 (MFS2), and Thoracic Aortic Aneurysms and Dissections (TAAD). In addition, some mutations lead to Shprintzen-Goldberg syndrome which is characterized by skeletal deformities and intellectual disabilities in addition to the cardiovascular involvement, or vascular Ehlers-Danlos Syndrome (vEDS) that is associated with spontaneous rupture of the main arteries and internal organs. Furthermore, Multiple Self-healing Squamous Epithelioma (MSSE), a rare familial skin cancer, is linked to mutations in these genes. This significant phenotypic variability observed in these disorders could be attributed to various factors, ranging from the nature of the mutation including its location within the protein, the variable functional impact of the mutations (hypomorphicity), the level of disruption to the intricate interactions between signaling pathways, and the influence of modifier genes or environmental factors. In addition to haploinsufficiency, the impairment of TGFβ signaling could be exacerbated in other scenarios, such as the dominant-negative effects, in which a mutant allele disrupts the normal activity of the wild-type protein by forming non-functional receptor oligomers, hindering their trafficking. This review sheds light on these hereditary disorders, highlighting the broad spectrum of their clinical presentations associated with mutations in the same gene, their pathophysiology, and underlying molecular mechanisms. Most crucially, it underscores the critical gaps in our current understanding while proposing compelling directions for future research. This review also emphasizes the pressing need to unravel the complex genotype-phenotype correlations, which could pave the way for more precise diagnostic and therapeutic strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1580274"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologically targeting Schwann cells to improve regeneration following nerve damage.","authors":"Alaa A Alhamdi, Shona Mackie, Ryan P Trueman, Melissa L D Rayner","doi":"10.3389/fcell.2025.1603752","DOIUrl":"10.3389/fcell.2025.1603752","url":null,"abstract":"<p><p>Schwann cells provide essential support for nerve growth and survival following peripheral nerve damage by producing various growth factors and other signalling molecules. Modulating the proliferation, differentiation, migration, or myelination of Schwann cells could result in accelerated repair and regeneration of injured nerves, ultimately leading to improved motor and sensory function. Therefore, Schwann cells are commonly advocated as therapeutic targets for nerve damage, which could be mediated by pharmacological intervention. This review discusses how compounds such as growth factors, hormones, and small molecules can regulate intracellular signalling pathways involved in modulating Schwann cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1603752"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics-based screening and validation of PANoptosis-related biomarkers in periodontitis.","authors":"Qing Sun, JinYue Hu, RuYue Wang, ShuiXiang Guo, GeGe Zhang, Ao Lu, Xue Yang, LiNa Wang","doi":"10.3389/fcell.2025.1619002","DOIUrl":"10.3389/fcell.2025.1619002","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is the most prevalent chronic inflammatory disease affecting the periodontal tissues. PANoptosis, a recently characterized form of programmed cell death, has been implicated in various pathological processes; however, its mechanistic role in periodontitis remains unclear. This study integrates multi-omics data and machine learning approaches to systematically identify and validate key PANoptosis-related biomarkers in periodontitis.</p><p><strong>Methods: </strong>Periodontitis-related microarray datasets (GSE16134 and GSE10334) were obtained from the GEO database, and PANoptosis-related genes were retrieved from GeneCards. Differential gene expression analysis was performed using the GSE16134 dataset, followed by weighted gene co-expression network analysis (WGCNA) to identify relevant gene modules. The intersection of differentially expressed genes and WGCNA modules was used to define differentially expressed PANoptosis-related genes (PRGs). Protein-protein interaction (PPI) networks of these PRGs were constructed using the STRING database and visualized with Cytoscape. Subnetworks were identified using the MCODE plugin. Key genes were selected based on integration with rank-sum test results. Functional enrichment analysis was performed for these key genes. Machine learning algorithms were then applied to screen for potential biomarkers. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and box plots. The relationship between selected biomarkers and immune cell infiltration was explored using the CIBERSORT algorithm. Finally, RT-qPCR was conducted to validate biomarker expression in clinical gingival tissue samples.</p><p><strong>Results: </strong>Through comprehensive bioinformatics analysis and literature review, ZBP1 was identified as a PANoptosis-related biomarker in periodontitis. RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).</p><p><strong>Conclusion: </strong>This study provides bioinformatic evidence linking PANoptosis to periodontitis. ZBP1 was identified as a key PANoptosis-related biomarker, suggesting that periodontitis may involve activation of the ZBP1-mediated PANoptosome complex.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1619002"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA CHRF: molecular mechanisms and therapeutic potentials in cardiovascular diseases, cancers and fibrosis.","authors":"Jie Mou, Chuntao Luo, Wen Zhang, Yin Shao, Juan Pei, Yaqin Chen, Xin Guo, Yonghong Fan, Hongyu Sun","doi":"10.3389/fcell.2025.1573723","DOIUrl":"10.3389/fcell.2025.1573723","url":null,"abstract":"<p><p>Long non-coding RNAs (LncRNA), exceeding 200 nucleotides in size, have emerged as important regulators of genes involved in multiple biological functions including cell growth, migration, invasion, drug resistance and apoptosis. They are increasingly being explored in human diseases. Notably, the recently identified LncRNA Cardiac hypertrophy-related factor (CHRF) has gained attention for its involvement in the molecular mechanisms of various diseases. CHRF was originally identified as a contributive LncRNA in cardiovascular diseases. Subsequent studies also revealed that it exerts an important role in promoting fibrosis and drug resistance. However, CHRF exhibits oncogenic functions in numerous cancers, including Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Ovarian cancer (OC), Gastric cancer (GC), indicating its crucial roles in cancer progression. CHRF exhibits tremendous potential as both therapeutic target and diagnostic biomarker, particularly in cardiomyopathy, fibrosis, and cancer. To enhance our comprehensive understanding, this review synthesizes the pathophysiological mechanisms associated with CHRF and discusses its biological significance and clinical implication. Additionally, This review provides a comprehensive discussion on therapeutic strategies based on Non-coding RNA targets and discuss the potential of targeting CHRF, which is expected to offer readers a research approach for identifying the correct target strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1573723"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning developed an immune evasion signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma.","authors":"Dongxiao Ding, Gang Huang, Liangbin Wang, Ke Shi, Junjie Ying, Wenjun Shang, Li Wang, Chong Zhang, Maofen Jiang, Yaxing Shen","doi":"10.3389/fcell.2025.1622345","DOIUrl":"10.3389/fcell.2025.1622345","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide and a major cause of cancer-related deaths. The advancement of immunotherapy has expanded the treatment options for LUAD. However, the clinical outcomes of LUAD patients have not been as anticipated, potentially due to immune escape mechanisms.</p><p><strong>Methods: </strong>An integrative machine learning approach, comprising ten methods, was applied to construct an immune escape-related signature (IRS) using the TCGA, GSE72094, GSE68571, GSE68467, GSE50081, GSE42127, GSE37745, GSE31210 and GSE30129 datasets. The relationship between IRS and the tumor immune microenvironment was analyzed through multiple techniques. <i>In vivo</i> experiments were performed to investigate the biological roles of the key gene.</p><p><strong>Results: </strong>The model developed by Lasso was regarded as the optional IRS, which served as an independent risk factor and had a good performance in predicting the clinical outcome of LUAD patients. Low IRS-based risk score indicated higher level of NK cells, CD8⁺ T cells, and immune activation-related functions. The C-index of IRS was higher than that of many developed signatures for LUAD and clinical stage. Low risk score indicated had a lower tumor escape score, lower TIDE score, higher TMB score and higher CTLA4&PD1 immunophenoscore, suggesting a better immunotherapy response. Knockdown of PVRL1 suppressed tumor cell proliferation and colony formation by regulating PD-L1 expression.</p><p><strong>Conclusion: </strong>Our study developed a novel IRS for LUAD patients, which served as an indicator for predicting the prognosis and immunotherapy response.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1622345"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer.","authors":"Qijing Wang, Kai Li, Liang Li, Qin Li, Yanyu Qi, Kai Liu, Hang Yuan, Ping Lin","doi":"10.3389/fcell.2025.1584630","DOIUrl":"10.3389/fcell.2025.1584630","url":null,"abstract":"<p><p>Cancer represents a serious threat to human health and life. Despite recent advances in the cancer therapy that significantly extend patient survival, many individuals still undergo drug resistance, even to multiple chemotherapeutic drugs, known as multidrug resistance (MDR). MDR causes the treatment failure and promotes the risk of tumor recurrence and metastasis, which has been a critical clinical challenge. The molecular mechanisms for cancer cells developing MDR are complex and largely unclarified. ATP-binding cassette (ABC) transporters-mediated enhanced drug efflux and glucose metabolic reprogramming have been recently identified as key factors that limit drug efficacy. In addition to regulating glucose metabolism, several glycolytic enzymes exhibit aberrant cellular localization, including translocation to the nucleus, cell membrane or mitochondria, which imparts their non-classical pro-oncogenic functions to facilitate tumor progression and MDR. In this review, we summarize the roles and molecular insights of glycometabolic enzymes in MDR progression and discuss existing therapeutic strategies of targeting glucose metabolic enzymes for overcoming MDR.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1584630"},"PeriodicalIF":4.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large language models in the management of chronic ocular diseases: a scoping review.","authors":"Jiatong Zhang, Xiaoxi Song, Bocheng Tian, Mingke Tian, Zhichang Zhang, Jing Wang, Ting Fan","doi":"10.3389/fcell.2025.1608988","DOIUrl":"10.3389/fcell.2025.1608988","url":null,"abstract":"<p><p>Large language models, a cutting-edge technology in artificial intelligence, are reshaping the new paradigm of chronic ocular diseases management. In this study, we comprehensively examined the current status and trends in the application of large language models in major blinding chronic ocular diseases such as glaucoma, cataract, and diabetic retinopathy through a systematic scoping review approach. We conducted this review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extended to characterize the application of large language models in the field of chronic ocular diseases. The study reveals that large language models demonstrate comparable efficacy to experts in disease screening, diagnostic decision-making, personalized precision treatment recommendation, and accessibility of healthcare resources by integrating multimodal clinical data. However, the application of the technology still faces a triple challenge: (1) the limitation of model generalization ability due to the multimodal nature of clinical data; (2) the ethical controversy caused by the insufficient interpretability of algorithms; and (3) the lack of a standardized validation framework. Future directions emphasize the need for specialized model training, multimodal algorithm optimization, the establishment of a multinational multicenter clinical validation platform, and the construction of an ethical framework for dynamic regulation. Large language models are expected to evolve from an assisted decision-making tool to a core component of precision medicine for chronic ocular diseases, and ultimately to achieve an ecosystem of energy-efficient full-cycle management of chronic ocular diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1608988"},"PeriodicalIF":4.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX9 mediates the phenotypic transformation of vascular smooth muscle cells in restenosis after carotid artery injury.","authors":"Chuan Jiang, Jiasen Ye, Jie Huang, Yang Gao, Hong Chen, Fuqiang Guo, Lei Guo, Xiaofan Yuan","doi":"10.3389/fcell.2025.1592594","DOIUrl":"10.3389/fcell.2025.1592594","url":null,"abstract":"<p><p>In-stent restenosis (ISR) remains a significant public health challenge globally, as millions of stents are implanted annually. Elucidating the mechanisms underlying ISR is essential for developing effective preventive and therapeutic strategies. In this study, we identified SOX9, a transcription factor, as a key factor involved in the pathogenesis of ISR. Morphological and histological analyses of human carotid atherosclerotic plaques revealed high expression of SOX9 at the interface between the fibrous cap (FC)-predominantly composed of α-smooth muscle actin (α-SMA)-positive vascular smooth muscle cells (VSMCs)-and the lipid-rich necrotic core (LRNC), enriched with CD68-positive macrophages. This region is characterized by a high frequency of phenotypic transformation of VSMCs. Using a carotid artery balloon injury model, we observed high expression of SOX9 in the neointima, and SOX9 knockdown significantly attenuated intimal hyperplasia. <i>In vitro</i>, SOX9 knockdown in primary VSMCs suppressed platelet-derived growth factor-BB (PDGF-BB)-induced phenotypic transformation, proliferation, and migration. Further studies using CUT&Tag analysis indicated that PDGF-BB promotes the AMPK signaling pathway, leading to the nuclear translocation of SOX9. A dual-luciferase reporter assay revealed that SOX9 directly binds to the motif of the signal transducer and activator of transcription 3 (STAT3) promoter, thereby enhancing the phenotypic transformation of VSMCs. This study uncovered a novel molecular mechanism in which AMPK-mediated SOX9 activation facilitates its interaction with STAT3 to regulate the transformation, proliferation, and migration of VSMCs. These findings suggest that targeting the SOX9-STAT3 axis can serve as a promising therapeutic strategy for the prevention and treatment of ISR.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1592594"},"PeriodicalIF":4.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: The role of enhancers in cancer.","authors":"Sonia V Forcales","doi":"10.3389/fcell.2025.1550404","DOIUrl":"https://doi.org/10.3389/fcell.2025.1550404","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1550404"},"PeriodicalIF":4.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}