Cellular and Molecular Life Sciences最新文献

Correction: Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-28 DOI: 10.1007/s00018-024-05569-6

Qi Qi, Yi Wang, Xiaochen Wang, Junying Yang, Yan Xie, Jie Zhou, Xiaoxia Li, Baoli Wang

引用次数: 0

METTL3-dependent m6A methylation of circCEACAM5 fuels pancreatic cancer progression through DKC1 activation.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-27 DOI: 10.1007/s00018-025-05653-5

Jie Zhang, Wenxue Sun, Wenda Wu, Zihui Qin, Ben Wei, Tushuai Li

{"title":"METTL3-dependent m6A methylation of circCEACAM5 fuels pancreatic cancer progression through DKC1 activation.","authors":"Jie Zhang, Wenxue Sun, Wenda Wu, Zihui Qin, Ben Wei, Tushuai Li","doi":"10.1007/s00018-025-05653-5","DOIUrl":"10.1007/s00018-025-05653-5","url":null,"abstract":"Background: Pancreatic cancer is highly lethal and has a poor prognosis. Research has highlighted the role of circular RNAs and m6A methylation in cancer progression. METTL3, a key m6A methyltransferase, is linked to various cancers, but its interaction with circular RNAs in pancreatic cancer is unclear. This study examined the role of circCEACAM5 in pancreatic cancer, particularly its regulation by METTL3-mediated m6A methylation and interaction with effectors such as DKC1.Methods: circCEACAM5 expression in pancreatic cancer tissues and cell lines was evaluated via RT‒qPCR. Its characteristics were validated through Sanger sequencing, stability assays, and FISH. Functional assays (CCK-8, EdU, Transwell, and flow cytometry) were conducted in AsPC-1 cells, and in vivo tumor models were established. m6A modification was analyzed via bioinformatics tools and m6A-specific immunoprecipitation, while RNA pull-down assays were used to examine the interaction of circCEACAM5 with METTL3 and DKC1.Results: circCEACAM5 was significantly upregulated in pancreatic cancer and correlated with poor clinical outcomes. CircCEACAM5 promoted cell proliferation, invasion, and migration while inhibiting apoptosis both in vitro and in vivo. METTL3-mediated m6A methylation of circCEACAM5 was confirmed, and METTL3 knockdown reversed the effects of circCEACAM5 silencing on the malignant behavior of pancreatic cancer cells. circCEACAM5 interacted with DKC1, and DKC1 overexpression reversed the effects of circCEACAM5 knockdown on the malignant behavior of pancreatic cancer cells.Conclusion: METTL3-mediated m6A methylation of circCEACAM5 drives pancreatic cancer progression by increasing DKC1 expression, suggesting potential new therapeutic targets for this aggressive malignancy.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"132"},"PeriodicalIF":6.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717804","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}

引用次数: 0

Microglia regulate myelin clearance and cholesterol metabolism after demyelination via interferon regulatory factor 5.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-26 DOI: 10.1007/s00018-025-05648-2

Alejandro Montilla, Alazne Zabala, Ibai Calvo, Marina Bosch-Juan, Irene Tomé-Velasco, Paloma Mata, Mirjam Koster, Amanda Sierra, Susanne M Kooistra, Federico N Soria, Bart J L Eggen, Olatz Fresnedo, José Andrés Fernández, Vanja Tepavcevic, Carlos Matute, María Domercq

{"title":"Microglia regulate myelin clearance and cholesterol metabolism after demyelination via interferon regulatory factor 5.","authors":"Alejandro Montilla, Alazne Zabala, Ibai Calvo, Marina Bosch-Juan, Irene Tomé-Velasco, Paloma Mata, Mirjam Koster, Amanda Sierra, Susanne M Kooistra, Federico N Soria, Bart J L Eggen, Olatz Fresnedo, José Andrés Fernández, Vanja Tepavcevic, Carlos Matute, María Domercq","doi":"10.1007/s00018-025-05648-2","DOIUrl":"10.1007/s00018-025-05648-2","url":null,"abstract":"Interferon regulatory factor 5 (IRF5) is a transcription factor that plays a role in orchestrating innate immune responses, particularly in response to viral infections. Notably, IRF5 has been identified as a microglia risk gene linked to multiple sclerosis (MS), but its specific role in MS pathogenesis remains unclear. Through the use of Irf5-/- mice, our study uncovers a non-canonical function of IRF5 in MS recovery. Irf5-/- mice exhibited increased damage in an experimental autoimmune encephalomyelitis (EAE) model and demonstrated impaired oligodendrocyte recruitment into the lesion core following lysolecithin-induced demyelination. Transcriptomic and lipidomic analyses revealed that IRF5 has a role in microglia-mediated myelin phagocytosis, lipid metabolism, and cholesterol homeostasis. Indeed, Irf5-/- microglia phagocytose myelin, but myelin debris is not adequately degraded, leading to an accumulation of lipid droplets, cholesterol esters, and cholesterol crystals within demyelinating lesions. This abnormal buildup can hinder remyelination processes. Importantly, treatments that promote cholesterol transport were found to reduce lipid droplet accumulation and mitigate the exacerbated damage in Irf5-/- mice with EAE. Altogether, our study identified the antiviral transcription factor IRF5 as a key transcriptional regulator of lipid degradation and cholesterol homeostasis and suggest that loss of IRF5 function leads to pathogenic lipid accumulation in microglia, thereby obstructing remyelination. These data and the fact that Irf5 polymorphisms are significantly associated with MS, highlight IRF5 as a potential therapeutic target to promote regenerative responses.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"131"},"PeriodicalIF":6.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728944","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}

引用次数: 0

Spatiotemporal profiling of adhesion G protein-coupled receptors in developing mouse and human pancreas reveals a role for GPR56 in islet development.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-26 DOI: 10.1007/s00018-025-05659-z

Oladapo E Olaniru, Klaudia Toczyska, Nunzio Guccio, Stefanie Giera, Xianhua Piao, Aileen J F King, Peter M Jones, Shanta J Persaud

{"title":"Spatiotemporal profiling of adhesion G protein-coupled receptors in developing mouse and human pancreas reveals a role for GPR56 in islet development.","authors":"Oladapo E Olaniru, Klaudia Toczyska, Nunzio Guccio, Stefanie Giera, Xianhua Piao, Aileen J F King, Peter M Jones, Shanta J Persaud","doi":"10.1007/s00018-025-05659-z","DOIUrl":"10.1007/s00018-025-05659-z","url":null,"abstract":"Introduction: G protein-coupled receptors (GPCRs) are cell-surface proteins that are targeted therapeutically for a range of disorders, including diabetes. Adhesion GPCRs (aGPCRs) are the second largest class of the GPCR superfamily and some members of this family have been implicated in appropriate organ development. However, the role of aGPCRs in endocrine pancreas specification is not yet known.Methods: Here, we systematically characterised expression of mRNAs encoding aGPCRs and their ligands in developing mouse and human pancreas using our own and publicly available single-cell RNA sequencing and spatial transcriptomics data, and we conducted qPCR analysis of aGPCR expression in human pancreas at different gestational stages. We then investigated the role of GPR56 (ADGRG1), the most abundant aGPCR in pancreatic endocrine progenitors, in islet development using Gpr56 null mice and their wildtype littermates.Results: We demonstrated that aGPCRs are dynamically expressed during mouse and human pancreas development, with specific aGPCR mRNAs expressed in distinct endocrine, endothelial, mesenchymal, acinar, ductal, and immune cell clusters. aGPCR ligand mRNAs were mostly expressed by non-endocrine cells, and the most highly expressed receptor-ligand interacting mRNA pairs were those encoding GPR56 and COL3A1. Deletion of Gpr56 in neonatal mice was associated with an altered α-/β-/δ-cell ratio and reduced β-cell proliferation.Conclusion: Our data show that aGPCRs are expressed at key stages of human and mouse pancreas endocrine lineage decisions, and analysis of pancreases from Gpr56 knockout mice implicate this aGPCR in the development of a full complement of β-cells.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"129"},"PeriodicalIF":6.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728961","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}

引用次数: 0

Endophilin B1 is essential for maintaining cardiac function by regulating mitocytosis.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-26 DOI: 10.1007/s00018-025-05646-4

Jingyu Deng, Xiaoqian Chang, Xiaomeng Zhang, Congye Li, Guigao Guo, Haifeng Song, Yangzhi Zheng, Chenhao Zhang, Bo Yang, Chujie Zhang, Pingping Xing, Zheng Zhang, Tao Yin, Ling Tao, Shan Wang

{"title":"Endophilin B1 is essential for maintaining cardiac function by regulating mitocytosis.","authors":"Jingyu Deng, Xiaoqian Chang, Xiaomeng Zhang, Congye Li, Guigao Guo, Haifeng Song, Yangzhi Zheng, Chenhao Zhang, Bo Yang, Chujie Zhang, Pingping Xing, Zheng Zhang, Tao Yin, Ling Tao, Shan Wang","doi":"10.1007/s00018-025-05646-4","DOIUrl":"10.1007/s00018-025-05646-4","url":null,"abstract":"Endophilin B1 is a member of the Endophilin family and has been shown to be involved in apoptosis, mitochondrial morphological changes and autophagy. Although Endophilin B1 is highly expressed in the heart, its role in the maintenance of normal cardiac function and myocardial ischemia and reperfusion (I/R) injury remains unclear. Here, we found that Endophilin B1 deletion provoked spontaneous cardiac contractile dysfunction, cardiac hypertrophy and fibrosis at 16 weeks of age. Moreover, at 8 weeks of age, although spontaneous cardiac dysfunction in Endophilin B1 deletion mice had not developed, the deletion of Endophilin B1 exacerbated I/R-induced cardiac contractile dysfunction and cardiomyocyte death, whereas restoration of Endophilin B1 expression in the heart reduced I/R injury. Furthermore, we discovered that Endophilin B1 is indispensable for maintaining normal mitochondrial structure and function. In addition, we found that Endophilin B1 is localized in extracellular mitochondrion-containing vesicles and is required for mitocytosis, a process by which damaged mitochondria are disposed through extracellular vesicles. In conclusion, our study identified Endophilin B1 as an essential mitocytosis regulator for maintaining mitochondrial homeostasis and cardiac function. These findings suggest that Endophilin B1 is a novel therapeutic target for cardiac disorders such as I/R injury, myocardial infarction and heart failure.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"130"},"PeriodicalIF":6.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728938","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}

引用次数: 0

PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-24 DOI: 10.1007/s00018-025-05664-2

Yaoyue Qi, Cheng-Han Yu

{"title":"PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly.","authors":"Yaoyue Qi, Cheng-Han Yu","doi":"10.1007/s00018-025-05664-2","DOIUrl":"10.1007/s00018-025-05664-2","url":null,"abstract":"Podosomes are adhesion structures with densely-polymerized F-actin. While PI(3,4,5)P3 and Cdc42-GTP are known factors to trigger WASP-mediated actin polymerization at the macrophage podosome, their causal mechanism to activate WASP remains unclear. Here, we demonstrate that spatially elevated Cdc42-GTP is a downstream effector of local PI(3,4,5)P3 production at the podosome. We further examine the expression and distribution of 19 Cdc42 guanine exchange factors (GEFs) and identify VAV1 as the key PI(3,4,5)P3-dependent Cdc42 GEF. VAV1 is spatially enriched at the macrophage podosome, and the association of VAV1 with the membrane plays a critical role in upregulating its GEF activity. Reintroduction of wildtype VAV1, rather than the PI(3,4,5)P3-binding deficient or catalytically dead mutants restores the matrix degradation and chemotactic migration of VAV1-knockdown macrophage. Thus, the biogenesis of PI(3,4,5)P3 acts as an upstream signal to locally recruit VAV1 and in turn triggers the guanine nucleotide exchange of Cdc42. Elevated levels of Cdc42-GTP then promote WASP-mediated podosome assembly and macrophage chemotaxis.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"127"},"PeriodicalIF":6.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699861","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}

引用次数: 0

The HBV large envelope protein initiates virion assembly by recruiting capsids at membrane rich domains related to late endosome.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-24 DOI: 10.1007/s00018-025-05574-3

Florian Seigneuret, Sébastien Eymieux, Vanessa Sarabia-Vega, Roxane Lemoine, Julien Burlaud-Gaillard, Pierre Raynal, Christophe Hourioux, Camille Sureau, Philippe Roingeard, Hugues de Rocquigny

{"title":"The HBV large envelope protein initiates virion assembly by recruiting capsids at membrane rich domains related to late endosome.","authors":"Florian Seigneuret, Sébastien Eymieux, Vanessa Sarabia-Vega, Roxane Lemoine, Julien Burlaud-Gaillard, Pierre Raynal, Christophe Hourioux, Camille Sureau, Philippe Roingeard, Hugues de Rocquigny","doi":"10.1007/s00018-025-05574-3","DOIUrl":"10.1007/s00018-025-05574-3","url":null,"abstract":"A crucial step of HBV (Hepatitis B Virus) virion morphogenesis is the envelopment of the nucleocapsid by the viral envelope proteins, which is triggered by an interaction between the HBV core protein and the large HBV envelope protein. To document this protein-protein interaction, we co-expressed core and large HBV envelope (LHBs) in Huh-7 cells and subjected the cells to microscopy examination by Fluorescence Resonance Energy Transfer (FRET) and Transmission Electron Microscopy (TEM). Our results show that the sole expression of the core protein leads to assembly of capsids that remain individually isolated within the whole cell, but particularly within the nucleus. In the presence of LHBs, capsids were observed as large clusters in a membrane rich region peripheral to the nucleus. In this context, core-LHBs complex co-localize with markers of the late endosome/multivesicular bodies, this co-localization being driven by LHBs. These results thus show that LHBs binds to the core proteins when preassembled into capsid, at membranes of the late endosome, where the inner capsid and the outer envelope meet to assemble a virion.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"128"},"PeriodicalIF":6.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699863","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}

引用次数: 0

Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-21 DOI: 10.1007/s00018-025-05641-9

Ashwin Narayanan, Mirca S Saurty-Seerunghen, Jessica Michieletto, Virgile Delaunay, Arnaud Bruneel, Thierry Dupré, Chris Ottolenghi, Clément Pontoizeau, Lucrezia Ciccone, Andreas De La Vara, Ahmed Idbaih, Laurent Turchi, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier, Elias A El-Habr

{"title":"Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells.","authors":"Ashwin Narayanan, Mirca S Saurty-Seerunghen, Jessica Michieletto, Virgile Delaunay, Arnaud Bruneel, Thierry Dupré, Chris Ottolenghi, Clément Pontoizeau, Lucrezia Ciccone, Andreas De La Vara, Ahmed Idbaih, Laurent Turchi, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier, Elias A El-Habr","doi":"10.1007/s00018-025-05641-9","DOIUrl":"10.1007/s00018-025-05641-9","url":null,"abstract":"Recent studies show that metabolites, beyond their metabolic roles, can induce significant changes in cell behavior. Herein, we investigate the non-canonical role of nicotinamide (vitamin B3) on glioblastoma (GB) cell behavior. Nicotinamide induced senescence in GB cells, characterized by reduced proliferation, chromatin reorganization, increased DNA damage, enhanced beta-galactosidase activity, and decreased Lamin B1 expression. Nicotinamide-induced senescence was accompanied by an unexpected reprogramming of its metabolism, marked by simultaneous downregulated transcription of NNMT (nicotinamide N-methyltransferase) and NAMPT (nicotinamide phosphoribosyl-transferase). Nicotinamide effects on GB cells were mediated by decreased levels of SOX2. Consistently, analyses of patients' single cell transcriptome datasets showed that GB cells with low NNMT and NAMPT expression levels were enriched in gene modules related to senescence. Remarkably, senescent GB cells retained tumor-forming ability in vivo, albeit to a lesser extent compared to control cells. Further experiments at the single-cell level and transcriptomic analyses demonstrated that nicotinamide-induced senescence in GB cells is fully reversible. Overall, our findings identify a novel reversible senescent state in GB tumors and highlight the non-canonical role of nicotinamide as a key driver of cancer cell plasticity.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"126"},"PeriodicalIF":6.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673376","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}

引用次数: 0

CYLD links the TRAF6/sNASP axis to TLR4 signaling in sepsis-induced acute lung injury.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-20 DOI: 10.1007/s00018-025-05654-4

Yu-Chih Wu, Bing-Hua Su, Wun-Hao Cheng, Cheng-Tai Zou, Edward T H Yeh, Feng-Ming Yang

{"title":"CYLD links the TRAF6/sNASP axis to TLR4 signaling in sepsis-induced acute lung injury.","authors":"Yu-Chih Wu, Bing-Hua Su, Wun-Hao Cheng, Cheng-Tai Zou, Edward T H Yeh, Feng-Ming Yang","doi":"10.1007/s00018-025-05654-4","DOIUrl":"10.1007/s00018-025-05654-4","url":null,"abstract":"Sepsis-induced acute lung injury (ALI) involves severe lung dysfunction and leads to high morbidity and mortality rates due to the lack of effective treatments. The somatic nuclear autoantigenic sperm protein (sNASP)/tumor necrosis factor receptor-associated factor 6 (TRAF6) axis plays a crucial role in regulating inflammatory responses during sepsis through Toll-like receptor 4 (TLR4) signaling. However, it is unclear whether deubiquitinating enzymes affect the TRAF6/sNASP axis. In this study, we showed that cylindromatosis (CYLD) directly binds to the sNASP and prevents TRAF6 activation. When TLR4 is activated, phosphorylation of sNASP releases CYLD from the TRAF6/sNASP complex, leading to TRAF6 autoubiquitination and the production of proinflammatory cytokines. To stop TRAF6 activation, a complex of sNASP, TRAF6, and CYLD is reformed once dephosphorylation of sNASP occurs by protein phosphatase 4 (PP4). Silencing sNASP negated the inhibitory effects of CYLD on interleukin (IL)-6 and TNF-α production after lipopolysaccharide (LPS) treatment. Similarly, the absence of CYLD also reduced PP4's negatively regulated production of proinflammatory cytokines, indicating that phosphorylation is crucial for the interaction between sNASP and CYLD as well as TRAF6 activation. Finally, mice infected with a recombinant adenovirus carrying the CYLD gene (Ad-CYLD WT), but not a mutation, showed significant reductions in cecal ligation and puncture (CLP)-mediated lung injury and proinflammatory cytokine production. In conclusion, CYLD alleviated sepsis-induced inflammation by interacting with the TRAF6/sNASP axis. These findings suggest that CYLD could be a potential therapeutic target for treating sepsis-induced ALI.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"124"},"PeriodicalIF":6.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662279","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}

引用次数: 0

R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation.

IF 6.2 2区生物学

Cellular and Molecular Life Sciences Pub Date : 2025-03-20 DOI: 10.1007/s00018-025-05658-0

Alessandro Cherubini, Clelia Pistoni, Maria Chiara Iachini, Cecilia Mei, Francesco Rusconi, Valeria Peli, Mario Barilani, Dorian Tace, Noemi Elia, Fabio Lepore, Vittoria Caporale, Lorenzo Piemonti, Lorenza Lazzari

{"title":"R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation.","authors":"Alessandro Cherubini, Clelia Pistoni, Maria Chiara Iachini, Cecilia Mei, Francesco Rusconi, Valeria Peli, Mario Barilani, Dorian Tace, Noemi Elia, Fabio Lepore, Vittoria Caporale, Lorenzo Piemonti, Lorenza Lazzari","doi":"10.1007/s00018-025-05658-0","DOIUrl":"https://doi.org/10.1007/s00018-025-05658-0","url":null,"abstract":"Mesenchymal stromal cells (MSC) play a critical role in the stem cell niche, a specialized microenvironment where stem cells reside and interact with surrounding cells and extracellular matrix components. Within the niche, MSC offer structural support, modulate inflammatory response, promote angiogenesis and release specific signaling molecules that influence stem cell behavior, including self-renewal, proliferation and differentiation. In epithelial tissues such as the intestine, stomach and liver, MSC act as an important source of cytokines and growth factors, but not much is known about their role in the pancreas. Our group has established a standardized technology for the generation of pancreatic organoids. Herein, we investigated the role of pancreatic mesenchymal stromal cells in the regulation of human pancreatic organoid proliferation and growth, using this 3D model in a co-culture system. We particularly focused on the capacity of pancreatic MSC to produce R-spondin factors, which are considered critical regulators of epithelial growth. We propose the development of a complex in vitro system that combines organoid technology and mesenchymal stromal cells, thereby promoting the assembloid new research era.","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"82 1","pages":"125"},"PeriodicalIF":6.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669290","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}

引用次数: 0