Frontiers in Cell and Developmental Biology最新文献

{"title":"Mechanotransduction and cell fate: from molecular sensors to multicellular self-organization.","authors":"María Del Carmen Estrada Elorza, Mónica Cruz-Lemini, Karina Martínez-Mayorga, Mariana G Martinez-Garfias, Ana Carolina Gómez-Carrillo, Alfonso Rios-Perez, Julio Granados-Montiel","doi":"10.3389/fcell.2026.1871354","DOIUrl":"https://doi.org/10.3389/fcell.2026.1871354","url":null,"abstract":"<p><p>Mechanical signals are now recognized as instructive cues that guide cell fate decisions with a precision comparable to classical morphogens. The identification of genetically encoded mechanosensors-including the PIEZO and TMC ion channel families, Transient Receptor Potential channels, and mechanosensitive adhesion complexes-has revealed how cells translate forces into transcriptional programs. In this review we integrate three levels of mechanotransduction biology: the molecular sensors that detect force, the intracellular signaling networks that convert sensing into gene expression, and the multicellular dynamics by which local mechanical interactions drive tissue self-organization. We discuss how substrate stiffness, applied tension, and cell-cell mechanical coupling regulates the differentiation of stem and progenitor cells across diverse lineages, with particular emphasis on the developing cardiovascular system as a paradigmatic mechanobiological organ: primitive blood flow instructs cardiac chamber morphogenesis, and mechanosensitive channels such as PIEZO1 are essential for vascular patterning. We also examine skeletal progenitor commitment and articulate an emerging conceptual distinction-the Regeneration-Specific Mechanosensor hypothesis-proposing that a defined subset of mechanosensors is dispensable during morphogenesis but becomes essential during tissue repair, with TRPA1 as the prototypical example. Structural and computational insights into channel gating, together with engineered mechanical environments for directing stem cell fate, provide a translational bridge toward regenerative therapeutics in cardiovascular and musculoskeletal medicine. Outstanding questions include the hierarchy of mechanosensors during lineage commitment, the mechanical logic of multicellular symmetry breaking, and the translational potential of regeneration-specific mechanosensitive drug targets. We propose that integrating molecular, cellular, and tissue-scale mechanobiology offers a unifying framework for understanding cell fate decisions in both development and regenerative medicine.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1871354"},"PeriodicalIF":5.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790297","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":"Unravelling the nexus of non-coding RNAs in cancer stemness and therapeutic drug resistance.","authors":"Song Chen, Tikam Chand Dakal, Ravi Bhushan, Dilip Kumar Arya, Bhaskar Gogoi, Abhishek Kumar, Ingo G H Schmidt-Wolf, Amit Sharma, Meiling Chen","doi":"10.3389/fcell.2026.1870002","DOIUrl":"https://doi.org/10.3389/fcell.2026.1870002","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) play a pivotal role in tumor initiation, progression, and therapy resistance. Emerging evidence suggests that non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), intricately regulate CSC properties. This article reviews current knowledge on the intricate interplay between ncRNAs, genetic and epigenetic factors having role in cancer stemness and associated phenotypes. We have also identified key stemness- and EMT-associated genes, including <i>OCT4</i>, <i>SOX2</i>, <i>NANOG</i>, <i>KLF4</i>, <i>CD44</i>, <i>ALDH1A1</i>, <i>BMI1</i>, <i>ZEB1</i>, <i>ZEB2</i>, <i>SNAIL</i>, <i>SLUG</i>, and <i>TWIST1</i> that are regulated by ncRNAs in different cancer types. Additionally, we have described how ncRNA-mediated regulation of these genes influences major signaling pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/AKT/mTOR, JAK/STAT, NF-κB, Hippo/YAP, and TGF-β signaling. The mir-21, miR-34, miR-200, and let-7 families target self-renewal and epithelial-to-mesenchymal transition while lncRNAs like H19, HOTAIR, and MALAT1 remodel the regulatory and epigenetic landscape of cancer stem cells. Understanding the interplay between ncRNAs and CSCs offers new insights into potential targeted therapies for combating aggressive and therapy-resistant cancers. Additionally, combining ncRNA interventions with conventional modalities such as chemotherapy, epigenetic drugs along with the advance nanotechnology-based drug delivery systems could result into synergistic outcomes. However, delivery, efficacy, and safety challenges remain. Overall, the ncRNA-cancer stemness interplay warrants therapeutic advancements and clinical translation towards a promising treatment personalization.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1870002"},"PeriodicalIF":5.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790261","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":"SLight-Net: a lightweight spectral-layer aware network for retinal disease detection based on optical coherence tomography.","authors":"Yixiang Yao, Jin Hong, Rongli Zhang, Junhua Hu, Libin Lu, Peixin Tan, Zhongbiao Xu, Shuhua Luo","doi":"10.3389/fcell.2026.1908247","DOIUrl":"https://doi.org/10.3389/fcell.2026.1908247","url":null,"abstract":"<p><strong>Background: </strong>Retinal diseases are a major cause of preventable visual impairment, and optical coherence tomography (OCT) provides high-resolution cross-sectional imaging for retinal assessment. However, reliable interpretation of OCT B-scans remains challenging because of speckle noise, subtle layer-wise changes, and visually similar pathological patterns.</p><p><strong>Methods: </strong>We propose SLight-Net, a lightweight spectral-layer aware network for retinal OCT classification. The model is built on a compact three-stage convolutional backbone and incorporates two OCT-specific modules. The Frequency-Aware Spectral-Spatial Encoder (FASE) integrates local convolution, dilated contextual modeling, and learnable spectral modulation to capture multi-scale structural and frequency-aware retinal features. The Retinal Layer Depth Attention (RLDA) module further introduces a depth-direction anatomical prior to recalibrate feature responses along retinal layers. Deep supervision and exponential moving-average weight updating are used to improve optimization stability.</p><p><strong>Results: </strong>On the OCT-C8 benchmark, SLight-Net achieves 98.21% classification accuracy with only 1.204M parameters. Additional evaluation on OCT2017 shows 99.30% accuracy, suggesting that the model maintains stable performance under a different class setting while remaining compact.</p><p><strong>Conclusion: </strong>These findings indicate that OCT-specific spectral and layer-aware priors can support efficient retinal disease classification without relying on large generic backbones, providing a practical basis for lightweight computer-aided OCT analysis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1908247"},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790255","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":"Understanding cancer as a systemic disease through comprehension of neural stemness as the core property of cancer cell and the basic rules it dictates.","authors":"Ying Cao","doi":"10.3389/fcell.2026.1843646","DOIUrl":"https://doi.org/10.3389/fcell.2026.1843646","url":null,"abstract":"<p><p>Cancer is a systemic disease with multilayered complexity. Some theories/hypotheses have been proposed to explain cancer. They are successful in explaining certain aspects of cancer, but meet serious challenges in other aspects. Inappropriate understanding of cancer cell and cancer complexity also hinders the development of more effective strategies of cancer therapy. My previous studies demonstrated that the core property of cancer (tumorigenic) cells is neural stemness. The finding led to the subsequent discovery about the central role of neural stemness during tumorigenesis and a paradigm that can hopefully explain systemic complexity of cancer as a whole. In the review, I summarize the evidence from research of evolutionary, developmental and cancer biology supporting that neural stemness, representing the general stemness predestined by its evolutionary advantage, determines both pluripotency and tumorigenicity, the key cellular properties underlying developmental and cancer biology, respectively. I made detailed discussions about the central role of neural stemness in understanding the core property and phenotypic traits of cancer cell and in understanding phenotypic heterogeneity in cancer. These pieces of evidence and discussions reveal that cancer is the manifestation of the power of basic rules dictating both embryogenesis and tumorigenesis. Briefly, acquiring neural stemness, hence a pluripotent state in ectodermal cells during embryogenesis, leads to neural development and body axis formation, i.e., embryonic neural induction, and ectopic neural induction causes a conjoined twin (secondary body axis); whereas acquirement of neural stemness, hence a pluripotent state in cells of a postnatal animal/human, results in a degenerated conjoined twin-like structure, i.e., a tumor. Tumors as conjoined twin-like structures formed in postnatal animals/humans helps understand the complex crosstalks within tumors and crosstalks between tumors and hosts. Moreover, neural stemness being the core property of cancer cell should account for the inverse correlation between cancer and neurodegeneration, and the neurodegeneration effect in patients after cancer therapies. Due to the central role of neural stemness in contributing to tumorigenesis, novel strategies of cancer therapy can be developed by targeting neural stemness using the principle of pluripotent cell differentiation. In addition, some essential issues worth considering in cancer research are also discussed.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1843646"},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790298","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 (osteopontin): a key regulator orchestrating cancer progression and non-cancerous pathologies - therapeutic opportunities and future directions.","authors":"Bo Pang, Huan Sun, Mingyu Ouyang, Cong Hu","doi":"10.3389/fcell.2026.1912468","DOIUrl":"https://doi.org/10.3389/fcell.2026.1912468","url":null,"abstract":"<p><p>Secreted Phosphoprotein 1 (SPP1) is a multifaceted matricellular glycoprotein that mediates diverse biological processes via integrin and CD44 receptor signaling. While its profound contributions to tumor progression and metastasis are extensively documented, emerging evidence underscores its pivotal roles across diverse non-cancerous conditions, including pregnancy-related complications, fibrotic diseases and neurological disorders. Crucially, SPP1 exhibits functional pleiotropy, orchestrating angiogenesis and epithelial-mesenchymal transition, while modulating immunosuppression. These collective actions drive disease progression, establishing SPP1 as a compelling therapeutic target. This review synthesizes current understanding of SPP1 biology, highlighting mechanistic insights imperative for translating its therapeutic potential into safe, precision-targeted interventions against diverse SPP1-driven pathologies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1912468"},"PeriodicalIF":5.3,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790271","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":"Age-dependent functional and transcriptional differences in intestinal mesenchymal stromal cells during early postnatal development in piglets.","authors":"Hammed Ayansola, Younggeon Jin","doi":"10.3389/fcell.2026.1847165","DOIUrl":"https://doi.org/10.3389/fcell.2026.1847165","url":null,"abstract":"<p><strong>Introduction: </strong>Intestinal mesenchymal stromal cells (iMSCs) regulate postnatal epithelial development, yet their temporal dynamics remain poorly defined in early postnatal piglets. Here, we investigated functional and transcriptional changes in jejunal iMSCs isolated from 0-, 7-, and 21-Day-old piglets.</p><p><strong>Methods and results: </strong>In an enteroid-iMSC coculture system, Day 0 iMSCs supported predominantly cystic enteroids with the highest surface area and proliferation index, whereas Day 7 iMSCs increased multi-budded enteroid morphology with intermediate proliferation, showing age-dependent differences in iMSC-mediated epithelial growth modulation. Relative real-time qPCR revealed that these functional differences aligned with niche-associated expression patterns in iMSCs. Specifically, RSPO3 level was highest at Day 0, BMP4 and PDGFRα expression peaked at Day 7, and WNT and BMP antagonists (SFRP1 and GREM1, respectively) increased in Day 21 iMSC samples. Bulk RNA sequencing further revealed shifts in iMSC transcriptomes across developmental stages, with Day 7 iMSCs exhibiting a transitional transcriptional profile enriched for genes associated with cytoskeletal reorganization and cell fate regulation compared with Day 0 iMSCs. Notably, pathway enrichment and gene set analyses identified multiple calcium channel genes and related pathways in Day 7 iMSCs compared with Day 0 iMSCs. Short-term pharmacological inhibition of calcium channels in Day 7 iMSCs was associated with rapid changes in niche factor levels, including decreased BMP4 and increased RSPO3 and WNT expressions.</p><p><strong>Conclusion: </strong>Together, these findings suggest age-related functional and transcriptional differences in iMSCs across early postnatal intestinal development. Our results highlight that calcium channel-related processes may be associated with changes observed in the Day 7 iMSC profile, providing a framework for future studies on iMSC-epithelial interactions during early intestinal development in piglets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1847165"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790438","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":"Single-cell multi-omics reveals circulating B cell heterogeneity across diverse disease contexts.","authors":"Rui Gan, Yunshan Zhong","doi":"10.3389/fcell.2026.1897676","DOIUrl":"https://doi.org/10.3389/fcell.2026.1897676","url":null,"abstract":"<p><strong>Introduction: </strong>B cells play essential roles in adaptive immunity by producing antigen-specific antibodies and interacting with T cells. Single-cell RNA and BCR sequencing technologies have enabled high-resolution dissection of B cell heterogeneity across diverse disease contexts. Atypical B cells (ABCs) display complex and critical functions in human immunity, yet their transcriptional heterogeneity, BCR diversity, and context-specific roles remain incompletely understood.</p><p><strong>Methods: </strong>In this study, we performed an integrative reanalysis of public single-cell RNA sequencing and single-cell B cell receptor (BCR) sequencing data derived from human peripheral blood mononuclear cells (PBMCs) across four distinct clinical contexts, including systemic lupus erythematosus (SLE), immunotherapy-treated melanoma, human immunodeficiency virus (HIV) blip, and age-stratified influenza vaccination. We established a unified analytical framework integrating transcriptomic profiling, BCR embedding-based clustering, and connectivity analysis to systematically characterize circulating B cell transcriptional features, BCR connectivity, and the correlation between transcriptomic and BCR diversity.</p><p><strong>Results: </strong>Our analysis revealed substantial dynamics in B cell transcriptomics and BCR repertoires across diverse time points and conditions. Notably, ABCs exhibited dynamic fluctuations, strong activation and BCR signaling, and marked transcriptomic diversity in response to autoreactive antigens, immunotherapy, transient viremia, and vaccination, positioning them as critical mediators of B cell responses. By integrating ABCs across all conditions, we identified nine distinct ABC clusters exhibiting specific transcriptional signatures associated with chemotaxis, complement activation, T cell regulation, plasma cell differentiation, or progenitor-like states. These ABC clusters displayed either phenotype-specific or shared distribution patterns, along with varying degrees of B cell activation, BCR signaling, and BCR connectivity across different phenotypes, suggesting divergent functional roles of ABCs.</p><p><strong>Discussion: </strong>Collectively, our cross-context analysis provides a broad characterization of circulating B cell heterogeneity, BCR diversity, and their associations in diverse conditions, advancing the understanding of ABC functional roles in human diseases. These findings highlight the potential of ABCs as key modulators of B cell responses across autoimmune, cancer, infection, and vaccine contexts.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1897676"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790295","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":"Crosstalk between gut microbiota and RNA N6-methyladenosine modification in diabetic retinopathy.","authors":"Junyan Hu, Shuai Dong, Ziyi Yao, Ziqing Gao, Shengqun Jiang","doi":"10.3389/fcell.2026.1841882","DOIUrl":"https://doi.org/10.3389/fcell.2026.1841882","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults, with a pathogenesis that extends far beyond chronic hyperglycemia. This narrative review synthesizes current evidence to construct a comprehensive model of DR that integrates metabolic memory, epigenetic regulation, and systemic factors such as the gut-retina axis. Specifically, this review focuses on the bidirectional crosstalk between gut microbiota dysbiosis and host RNA N6-methyladenosine (m6A) modification as the central mechanism linking these factors. We examine how gut microbiota dysbiosis contributes to the initiation and progression of DR by influencing the host epigenetic landscape, particularly the dynamic RNA N6-methyladenosine (m6A) modification. Hyperglycemia and microbial dysbiosis collectively drive the dysregulation of m6A \"writers\" (e.g., METTL3/14), \"erasers\" (e.g., FTO, ALKBH5), and \"readers\" (e.g., YTHDF family), leading to stable alterations in the expression of genes involved in inflammation, oxidative stress, angiogenesis, and neurodegeneration, thereby establishing \"metabolic memory.\" The gut microbiota and its metabolites (including short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and tryptophan derivatives) not only modulate host m6A modification but are also themselves influenced by the host m6A machinery, forming a bidirectional \"microbiota-m6A\" regulatory axis. A deep understanding of this interaction network not only offers a new perspective on the complex pathological mechanisms underlying DR but also lays a theoretical foundation for developing novel microbiome- and epitranscriptome-based biomarkers and therapeutic strategies, such as probiotics, prebiotics, and small-molecule drugs targeting m6A enzymes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1841882"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790525","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":"Toll/IL-1 receptor domain-containing adaptor protein plays a crucial role in macrophage-mediated hepatic stellate cell activation in alcoholic liver disease.","authors":"Pramod Patidar, Alexander G Obukhov, Sheikh A Tasduq, Luciano Saso, Mirza S Baig","doi":"10.3389/fcell.2026.1883301","DOIUrl":"https://doi.org/10.3389/fcell.2026.1883301","url":null,"abstract":"<p><strong>Background: </strong>Alcoholic liver disease (ALD) remains a significant global health issue, marked by chronic liver injury and progressive accumulation of extracellular matrix (ECM), ultimately leading to fibrosis. A key driver of this fibrotic process is the activation of hepatic stellate cells (HSCs), largely influenced by inflammatory signals from immune cells-particularly macrophages. This study explores the specific signalling mechanisms in macrophages that contribute to HSC activation in the context of alcohol exposure, aiming to identify new therapeutic targets.</p><p><strong>Methods: </strong>To mimic the disease condition, THP-1-derived macrophages were stimulated with ethanol and lipopolysaccharide (LPS). Cytokine expression was quantified by RT-qPCR, while the activation of TIRAP, MAPKs, and fibrotic markers in THP-1-derived macrophages and LX-2 cells was evaluated by western blotting and immunofluorescence staining.</p><p><strong>Result: </strong>Activation was indicated by increased expression of pro-inflammatory and fibrogenic factors, including IL-1β, TNF-α, IL-6, TGF-β, and PDGF-α. Signalling analysis revealed heightened phosphorylation of TIRAP (Toll/IL-1 receptor domain-containing adaptor protein), along with activation of downstream MAPK pathways (p38, ERK, JNK) and NF-κB. The conditioned media from these activated macrophages was applied to HSC cultures, resulting in elevated levels of fibrotic markers such as α-smooth muscle actin (α-SMA) and collagen, confirming HSC activation. Importantly, silencing TIRAP in macrophages significantly reduced the expression of these markers in HSCs, suggesting a key role for TIRAP in driving fibrogenesis.</p><p><strong>Conclusion: </strong>Overall, these findings underscore the importance of TIRAP- mediated signalling in macrophages as a central mechanism in alcohol- induced liver fibrosis, and propose macrophage TIRAP as a promising target for therapeutic intervention in ALD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1883301"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790237","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":"SUMO2 deficiency impairs endogenous regulation of oxidative stress and apoptosis in myocardial ischemia-reperfusion injury.","authors":"Xiuying Zhang, Wei Zhao, Jia Zhao, Ni Fan, Yu Wang, Aimin Xu, Wei Yang, Jianhui Rong","doi":"10.3389/fcell.2026.1842772","DOIUrl":"https://doi.org/10.3389/fcell.2026.1842772","url":null,"abstract":"<p><strong>Introduction: </strong>Myocardial ischemia-reperfusion injury (MIRI) is a major obstacle in the treatment of myocardial infarction and is closely associated with oxidative stress and cardiomyocyte death. Although endogenous protective mechanisms are activated during ischemic stress, they are often insufficient to prevent injury. SUMOylation is an important post-translational modification involved in cellular stress adaptation, and SUMO2 may contribute to the endogenous cardioprotective response.</p><p><strong>Methods: </strong>To investigate the role of SUMO2 in MIRI, we generated heart-specific SUMO2 knockout (SUMO2-KO) mice by crossing SUMO2-loxP mice with Myh6-Cre mice and assessed cardiac injury after myocardial infarction. In parallel, adeno-associated virus-mediated SUMO2 overexpression was used to assess the protective effect of SUMO2. In H9c2 cells subjected to oxygen-glucose deprivation, SUMO2 silencing was performed to examine reactive oxygen species (ROS) production, Bax/Bcl-2 balance, apoptosis, and p53-associated signaling.</p><p><strong>Results: </strong>SUMO2-KO mice exhibited more severe myocardial injury and worse cardiac dysfunction after ischemic injury. In contrast, SUMO2 overexpression markedly attenuated cardiac damage. In H9c2 cells, SUMO2 silencing increased ROS production, disrupted the Bax/Bcl-2 balance, and enhanced apoptosis. These effects were accompanied by alterations in p53-associated signaling.</p><p><strong>Discussion: </strong>These findings suggest that SUMO2 is an important regulator of endogenous cardioprotection during MIRI and may represent a potential target for future investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1842772"},"PeriodicalIF":5.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790235","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}