Cell Communication and Signaling最新文献

{"title":"Caveolae in cancer: mechanochemical signaling in tumor progression, immunity, and therapy.","authors":"Wen Cai, Xinlei Li, Yifan Chen, Hanguang Hu, Jiawei Zhang","doi":"10.1186/s12964-026-03062-0","DOIUrl":"10.1186/s12964-026-03062-0","url":null,"abstract":"<p><p>Caveolae are specialized, flask-shaped invaginations of the plasma membrane enriched in cholesterol, sphingolipids, and other membrane lipids that serve as multifunctional hubs for signal transduction, endocytosis, and mechanosensing. Their formation and functions depend on the coordinated organization of lipid microdomains, caveolins (CAV1-3), cavins (CAVIN1-4), and regulatory proteins such as EHD2 and PACSIN2, which together enable caveolae to dynamically reorganize in response to mechanical and biochemical cues. Beyond their classical functions in membrane organization, caveolae influence tumor cell proliferation, invasion, and metabolic adaptation by modulating key signaling pathways and cytoskeletal dynamics. Emerging studies suggest that caveolae contribute to tumor immune regulation by affecting antigen processing, immune cell trafficking, and the trafficking and extracellular vesicle-mediated dissemination of immune checkpoint molecules such as PD-L1. Within the tumor microenvironment, caveolae act as mechanosensitive membrane reservoirs that buffer plasma membrane tension and translate extracellular stiffness, shear stress or solid pressure into intracellular signaling responses. Through these mechanisms, caveolae may shape tumor progression, immune evasion, and responses to therapy. In this review, we synthesize current advances in caveolae biology from structural, lipid-membrane, signaling, immunological, and mechanobiological perspectives, emphasizing caveolae as integrated mechanochemical organelles rather than isolated molecular components. We discuss how caveolae couple membrane tension, lipid organization, and signaling plasticity in cancer, and we highlight emerging translational opportunities and unresolved questions relevant to tumor progression, immune regulation, and therapy.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551034","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":"Pulmonary megakaryocytes orchestrate host defense via PcrV-induced NF-κB signaling in Pseudomonas aeruginosa infection.","authors":"Xiaolong Guo, Qian Dai, Xiping Liao, Yannan Ma, Hengqian Liu, Junzhi Xiong, Hua Yu, Yuanyuan Li, Kebin Zhang, Jianyun Zhou, Hongli Zhou","doi":"10.1186/s12964-026-03072-y","DOIUrl":"https://doi.org/10.1186/s12964-026-03072-y","url":null,"abstract":"<p><strong>Background: </strong>Megakaryocytes, beyond their classical role in platelet formation, are increasingly recognized as immune modulators. This study aimed to investigate the function and activation mechanisms of megakaryocytes during Pseudomonas aeruginosa (PA) infection, focusing on their interaction with bacterial toxins and innate immune pathways.</p><p><strong>Methods: </strong>This study evaluated the response of pulmonary megakaryocytes to PA-induced acute pneumonia in mice. Specifically, the activation status of pulmonary megakaryocytes was determined by flow cytometry and sorting, followed by RNA sequencing, combining Gene Ontology and Gene Set Enrichment Analysis. The expression of pro-inflammatory cytokines and chemokines within megakaryocytes after PA infection were detected by qPCR and fluorescent confocal imaging. The effect of megakaryocytes on the chemotaxis and recruitment of neutrophils and monocytes was demonstrated using chemotaxis assays. Additionally, purified PA toxins were injected into the lungs of mice in vivo or added to flow-sorted cells in vitro in order to induce inflammation and evaluate the response of megakaryocytes to a single PA toxin. The activation status of intracellular signaling pathways was verified through inhibitor-mediated blocking experiments.</p><p><strong>Results: </strong>PA infection significantly activates megakaryocytes, which promote the recruitment of phagocytes and enhance the host's defense against PA infection. The innate immune response in the lungs was diminished during the early stages of PA infection among the megakaryocytes depleted mice, resulting in increased bacterial load and higher mortality. Flow cytometry sorting followed by RNA sequencing indicated that megakaryocytes exhibit a typical pro-inflammatory phenotype, along with NF-κB pathways activation. Furthermore, the PA toxin PcrV was identified as a key NF-κB activator on megakaryocytes, as demonstrated by increased expression of inflammatory markers and chemokines in response to PcrV. Inhibition of NF-κB signaling attenuated this pro-inflammatory phenotype of megakaryocytes.</p><p><strong>Conclusions: </strong>This study provides new insights into how megakaryocytes shape the cytokine and chemokine landscape in the lung during PA infection. It highlights the intrinsic interactions between megakaryocytes and phagocytes during pathogen invasion, suggests that managing megakaryocyte activity could be a new strategy to enhance immune defense.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity-based proteomics analysis revealed that DNJ directly targeted ATP5F1 to alleviate high glucose induced cardiomyocyte injury.","authors":"Xue Li, Yiwei Chen, Huixin Yang, Xianjie Hou, Ruyu Wang, Baorui Cao, Jinxiang Han, Meina Yang","doi":"10.1186/s12964-026-03077-7","DOIUrl":"10.1186/s12964-026-03077-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) is a significant complication of diabetes mellitus, characterized by impaired cardiac function and mitochondrial injury. The natural alkaloid 1-deoxynojirimycin (DNJ) has exhibited cardioprotective potential; however, its specific molecular targets in cardiomyocytes are yet to be identified.</p><p><strong>Purpose: </strong>This work sought to discover the direct targets of DNJ in cardiomyocytes and elucidate the molecular mechanism behind its cardioprotective activity.</p><p><strong>Methods: </strong>We first established a cardiomyocyte injury model induced by high glucose. Next, activity-based protein profiling (ABPP) was employed to screen for proteins that directly bind to DNJ. The interactions between DNJ and candidate targets were verified using surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and molecular docking. Finally, the functional outcomes were validated through small interfering RNA (siRNA) knockdown and plasmid overexpression.</p><p><strong>Results: </strong>ABPP screening identified mitochondrial F0 complex subunit B1 (ATP5F1) as the principal binding target of DNJ. SPR analysis confirmed a high-affinity interaction between DNJ and ATP5F1 (Kd = 52.6 nM). Furthermore, CETSA demonstrated that this binding occurred in living cells. Treatment with DNJ (120 µg/mL) significantly ameliorated high glucose-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Knockdown of ATP5F1 via siRNA attenuated the protective effects of DNJ. Conversely, ATP5F1 overexpression potentiated these protective effects.</p><p><strong>Conclusions: </strong>ATP5F1 was identified as a direct functional target of DNJ for the first time. DNJ provides cardioprotection by mitigating mitochondrial malfunction, oxidative stress, and apoptosis via its direct interaction with ATP5F1. These findings collectively clarify a new mode of action for DNJ and offer a scientific basis for its possible therapeutic use in DCM.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521452","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":"Targeting the mevalonate pathway sensitizes multiple myeloma cells to bortezomib through induction of mitochondrial metabolic disruption.","authors":"Shuya Li, Na Hu, Xiaodong Li, Yuan Feng, Yunmeng Ran, Zhipeng Geng, Hua Wang, Jinheng Wang","doi":"10.1186/s12964-026-03076-8","DOIUrl":"10.1186/s12964-026-03076-8","url":null,"abstract":"<p><strong>Background: </strong>Multiple myeloma (MM) remains an incurable hematologic malignancy with bortezomib resistance representing a major therapeutic challenge. The mevalonate (MVA) pathway, a crucial metabolic cascade involved in cholesterol synthesis, has emerged as a potential target for cancer therapy.</p><p><strong>Methods: </strong>In this study, we first investigated the correlations between the MVA pathway and MM progression. Leveraging public databases, transcriptome sequencing, mass cytometry, as well as in vitro and in vivo experimental models, we further systematically evaluated the therapeutic efficacy and underlying mechanisms of statins, a class of clinically available MVA pathway inhibitors, for the treatment of MM.</p><p><strong>Results: </strong>Using microarray and sequencing datasets, we found that the MVA pathway is dysregulated in MM and correlated with poor prognosis, as core genes in this pathway were significantly dysregulated in MM patients. Statins directly inhibit MM cell viability, induce apoptosis, and up-regulate apoptosis-associated proteins. These effects of statins are associated with the activation of the ERK pathway. They also induce dysregulation of metabolism, oxidative stress, and autophagy in MM cells. Moreover, the combination of statins and bortezomib exerts a synergistic anti-MM effect both in vitro and in vivo.</p><p><strong>Conclusions: </strong>Our preclinical data suggest that the MVA pathway can serve as a therapeutic target for MM and the combination of statins, widely used and safe drugs in the clinic, with bortezomib offers a promising strategy to overcome bortezomib resistance and improve therapeutic outcomes for MM patients.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537659","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":"Dynamic m6A epitranscriptomic remodeling coordinates host transcriptional reprogramming during MPXV infection.","authors":"Ruixia Tang, Jindi Huang, Wenhai Yu, Shuaiyao Lu, Jienan Zhou, Kaiyun Ding, Junbin Wang, Cong Tang, Xiaoqing Fu, Tingfu Du, Qiangming Sun","doi":"10.1186/s12964-026-03090-w","DOIUrl":"10.1186/s12964-026-03090-w","url":null,"abstract":"<p><strong>Background: </strong>The global emergence of monkeypox virus (MPXV) highlights the urgent need for a deeper understanding of host-pathogen interactions. Although transcriptional responses to MPXV infection have been characterized, the role of epitranscriptomic regulation particularly N6‑methyladenosine (m6A) modification remains largely unexplored.</p><p><strong>Methods: </strong>We performed an integrated analysis of time‑series transcriptomic and m6A methylome profiles using whole blood samples collected from MPXV‑infected rhesus macaques at 7, 14, and 21 days post‑infection, with distinct animals used at each time point. Host gene expression and m6A modification dynamics were examined over the course of infection. Differential expression and differential m6A modification analyses were conducted, followed by integrative pathway and immune cell signature profiling.</p><p><strong>Results: </strong>MPXV infection induced sustained host reprogramming, characterized by suppression of immune pathways and activation of metabolic processes. A global increase in m6A modifications was observed, accompanied by upregulation of the methyltransferase METTL3 and downregulation of demethylases (FTO, ALKBH5) and readers (YTHDF1-3). Knockdown of METTL3 or YTHDF2 reduced viral replication, suggesting a proviral role for this regulatory circuit. Integrative analysis identified 38 genes with coordinated changes in both transcription and m6A modification across all three time points. Focusing on literature-curated pathogenic pathways, we further identified 11 dual-regulated host factors. Notably, DNAJB1 was the only gene shared between these two independent selection strategies. m6A peaks near transcription start sites and within 5'UTR positively correlated with gene expression, whereas coding region modifications showed weak negative correlations. Immune lineage signatures showed gradual declines in T cell, NK, and monocyte/macrophage signatures with a progressive increase in B cell signatures. Cross‑dataset comparison confirmed core m6A regulatory trends despite heterogeneity across tissues and viral strains.</p><p><strong>Conclusions: </strong>This study reveals m6A epitranscriptomic remodeling as a key correlate of the host response to MPXV infection and nominates DNAJB1 alongside the other 10 dual‑regulated genes as candidate host factors for further mechanistic investigation.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474417","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":"SPP1-positive macrophages drive trastuzumab resistance in HER2-positive breast cancer.","authors":"Donghui Wang, Guodong Li, Yajie Lu, Ruoxin Du, Xiangmei He, Jiahui Sun, Danxi Li, Siyuan Wang, Yimin Liu, Shuning Wang, Lan Hou, Juliang Zhang, Yuan Gao, Cun Zhang","doi":"10.1186/s12964-026-03075-9","DOIUrl":"10.1186/s12964-026-03075-9","url":null,"abstract":"<p><p>Trastuzumab-based HER2-targeted therapy remains the cornerstone treatment for HER2-positive breast cancer. However, its clinical efficacy is significantly modulated by the tumor microenvironment (TME). Our single-cell sequencing analysis of clinical samples revealed that patients with poor radiologic response after trastuzumab-based neoadjuvant therapy presented significant enrichment of TIGIT⁺ NK cells with high immune checkpoint expression, exhausted CD8⁺ T cells, and immunosuppressive regulatory T cells (Tregs). Further analyses leveraging cell-cell communication, spatial transcriptomics, and multiplex immunofluorescence showed that SPP1⁺ tumor-associated macrophages (SPP1⁺ TAMs) enrichment was associated with dysfunctional NK- and T-cell states in tumors from patients with poor radiologic response. Functional validation studies revealed that SPP1⁺ TAMs actively induced exhaustion phenotypes in both NK cells and CD8⁺ T cells, thereby impairing trastuzumab-dependent antibody-dependent cellular cytotoxicity (ADCC) and adaptive immune responses. In vivo experiments using humanized NCG murine models further confirmed the SPP1⁺ TAMs-mediated suppression of NK cell function. Significantly, HER2-positive breast cancer patients with elevated SPP1⁺ TAMs levels experienced both reduced efficacy of trastuzumab neoadjuvant therapy and diminished long-term survival prospects. In summary, our findings provide the first systematic characterization of TME remodeling following trastuzumab therapy, identifying SPP1⁺ TAMs as a potential driver of trastuzumab resistance. This work advances our understanding of microenvironmental mechanisms underlying trastuzumab resistance and suggests new therapeutic strategies targeting TAM-mediated immunosuppression.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474357","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":"Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.","authors":"Mei Wang, Yue Mi, Qinong Ye","doi":"10.1186/s12964-026-03080-y","DOIUrl":"10.1186/s12964-026-03080-y","url":null,"abstract":"<p><p>Breast cancer (BC) development is influenced by multifactorial mechanisms. Despite significant advancements in early diagnostic techniques and comprehensive therapeutic approaches, BC continues to pose a substantial threat to women's health, exhibiting persistently high incidence and mortality rates. The Notch signaling pathway, a highly conserved evolutionary pathway initially identified in Drosophila, has garnered extensive research interest and is implicated in the pathogenesis of diverse malignancies, including BC. However, accumulating evidence reveals a highly context-dependent role for Notch signaling in cancer, with documented functions ranging from oncogenic to tumor-suppressive depending on the specific cellular and microenvironmental context. Current evidence indicates that Notch1-4 display nonredundant functional divergence in BC. In this review, we discuss how receptor-specific regulatory mechanisms shape distinct Notch1-4 signaling outputs and summarize the context-dependent functions and molecular mechanisms of Notch receptors across tumor-cell states, BC molecular subtypes, and tumor microenvironmental components. We also review current advances and limitations in pan-Notch inhibition and receptor-specific targeting strategies, aiming to provide clearer directions for future Notch receptor-targeted therapy in BC.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.","authors":"Jiayi Ye, Yijun Zhao, Shuyang Mao, Xingxing Li, Zitong Wang, Xin Li, Xinchen Xu, Minqi Tao, Chunhai Xiao, Qingqing Huang, Gang Huang, Wei Xie","doi":"10.1186/s12964-026-03084-8","DOIUrl":"10.1186/s12964-026-03084-8","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a dynamic and constantly evolving milieu surrounding cancer cells, comprising numerous components that influence tumor growth. The Carcinoembryonic Antigen-Related Cell Adhesion Molecule (CEACAM) family has been found to be abnormally expressed in various cancers, and recent studies have highlighted its critical role in shaping and regulating the TME. Several antibody drugs targeting the CEACAM family have been developed over the last years. However, due to the physiological expression of CEACAMs in normal tissues, most of these targeted agents have yielded unsatisfactory clinical trial outcomes, characterized by significant toxicity and limited efficacy. In view of this, enhancing therapeutic efficacy while reducing adverse effects has become a focal point of current research. This review systematically summarizes the structural features of the CEACAM family and the intrinsic mechanistic differences underlying their tumor-promoting effects, and discusses the limitations of existing clinical drugs. Based on antibody optimization strategies, we propose a conceptual framework of \"dual-recognition\" antibodies and elaborate on precision targeting approaches at three levels-epitope, molecular, and environmental-to provide directional guidance for future investigations.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474412","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":"Glycolysis drives vascular hyperpermeability in acute lung injury via lactate-GPR81 axis in endothelial cells.","authors":"Kun Chen, Kerui Fan, Jiao Wang, Xinyan Zan, Honghong Zhou, Jing Song, Yongqiang Yang, Kai Hu, Ying Zhi, Jingyuan Wan, Hongzhong Li, Sheng Cheng, Xiaojun Ren, Min Zhu, Yu Jiang, Gang Liu, Li Zhang","doi":"10.1186/s12964-026-03070-0","DOIUrl":"10.1186/s12964-026-03070-0","url":null,"abstract":"<p><p>A growing body of evidence suggests that enhanced glycolysis profoundly reprograms inflammatory response in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS), but the underlying mechanisms largely remain unclear. Lactate is the end-product of glycolysis, which has been recently found to function as a bioactive metabolite via G-protein coupled receptor 81 (GPR81). In the present study, the potential roles of lactate-GPR81 axis were investigated in mice with lipopolysaccharide (LPS)-induced ALI. The results indicated that LPS challenge increased the level of lactate in bronchoalveolar lavage fluid (BALF). Pharmacological suppression of glycolysis or inhibition of lactate dehydrogenase decreased lactate level and alleviated lung injury, but supplementation with lactate or a GPR81 agonist exacerbated lung injury. Global deletion of GPR81 or endothelial-specific deletion of GPR81, but not myeloid-specific deletion of GPR81, resulted in alleviated lung injury. In endothelial cells, the differentially expressed genes (DEGs) in RNA-seq after lactate supplementation were enriched in cAMP signaling pathway. Consistently, supplementation with lactate resulted in decline of cAMP, reduction of VE-cadherin and enhanced phosphorylation of myosin light chain 2 (MLC2) in endothelial cells, whereas knockdown of GPR81 reversed these effects. In addition, the modulation of lactate/GPR81 on cAMP, VE-cadherin and MLC2 was validated in GPR81 knockout mice. Importantly, the elevation of lactate is positively correlated with the degree of protein leakage, the level of proinflammatory cytokines in BALF and APACHE II score from patients with ARDS. Taken together, the present study suggests that endothelial GPR81 molecularly bridges glycolysis and inflammation, which drives microvascular hyperpermeability and the development of ALI.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474381","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 IGF2-ERK-Fos axis drives a Müller cell glial-mesenchymal transition-like response to disrupt retinal homeostasis in early myopia.","authors":"Jiaojiao Feng, Xiaoqi Gong, Yibo Han, Yunxiao Xie, Anfeng Luo, Hongtao Li, Wei Zhang, Jing Li, Xiaoyun Dong, Shuhan Li, Han Yu, Jike Song, Hongsheng Bi","doi":"10.1186/s12964-026-03088-4","DOIUrl":"10.1186/s12964-026-03088-4","url":null,"abstract":"<p><p>Myopia is increasingly recognized as a complex pathology involving retinal remodeling, yet the cellular mechanisms linking early visual stress to this process remain unclear. This study investigated whether Müller glial (MG) cells undergo a glial-mesenchymal transition (GMT)-like response in early myopia and identified the upstream signaling axis driving this transformation. We integrated single-cell and spatial transcriptomic analyses to construct a high-resolution atlas of retinal cell heterogeneity in a guinea pig model of form-deprivation myopia (FDM). Single-cell analysis revealed an expanded MG population (18.9% vs. 6.9%) and identified a disease-enriched Fos⁺ MG subcluster exhibiting a transcriptional signature of GMT and activated extracellular matrix (ECM) remodeling. IGF2 signaling was elevated in myopic MG cells and correlated with ERK/Fos activation. In vivo siIGF2 attenuated myopia progression, preserved retinal function/structure, suppressed MG activation/proliferation and GMT/ECM marker expression, and reduced inner limiting membrane abnormalities and retinal stiffening. Conversely, in vitro, rhIGF2 activated the ERK/Fos pathway, promoting proliferation, migration, GMT-like response, and collagen synthesis in MIO-M1 cells. These findings demonstrate that early myopia involves Fos⁺ MG-driven retinal remodeling via GMT-like response, coupling visual stress to ECM and mechanical changes. The IGF2-ERK-Fos axis is a key upstream driver of this pathology, presenting a novel target for intervention to preserve retinal homeostasis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":" ","pages":""},"PeriodicalIF":11.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474473","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}