Cellular and Molecular Life Sciences最新文献

{"title":"GATM alleviates sepsis-induced acute kidney injury via PDK4-mediated glycolytic reprogramming in renal tubular epithelial cells.","authors":"Ruhao Yang, Niandan Hu, Hairui Chen, Wenqiang Li, Ting Zheng","doi":"10.1007/s00018-026-06224-y","DOIUrl":"https://doi.org/10.1007/s00018-026-06224-y","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify a key target gene in proximal tubule cells (PTCs) of sepsis-induced acute kidney injury (S-AKI) and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>We screened and analyzed GEO datasets and identified a key gene, GATM, in S-AKI. An S-AKI mouse model was established via intraperitoneal injection of lipopolysaccharide (LPS), and HK-2 cells were used for in vitro experiments. The role of GATM was evaluated using adeno-associated virus (AAV)-mediated overexpression in mice and plasmid-mediated overexpression in HK-2 cells. To identify the downstream target genes of GATM, transcriptome sequencing was conducted. Pathological evaluation was performed using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. Protein levels were determined by Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) assays; Apoptosis was evaluated by TUNEL staining; Mitochondrial morphology and function were assessed by transmission electron microscopy (TEM), JC-1 and MitoSOX assays. Lactate concentration and cellular ATP levels were measured.</p><p><strong>Results: </strong>Through analysis of four datasets (GSE151658, GSE247727, GSE220812, and GSE139061), GATM was identified as a key gene in PTCs during S-AKI. GATM expression was downregulated in both S-AKI mice and LPS-stimulated HK-2 cells. In vivo, GATM overexpression improved renal function, alleviated tubular damage, decreased the expression of KIM-1, IL-6, Caspase-3, and 4-HNE, and reduced mitochondrial injury. In vitro, HK-2 cell viability was enhanced, TUNEL-positive cells were reduced, and damaged mitochondria were decreased. Transcriptome sequencing revealed that the PDK4-mediated glycolysis pathway was a downstream target of GATM. GATM overexpression downregulated PDK4 expression, reduced glycolytic enzyme levels (p-PDHA, HK2, LDHA, GLUT1) and lactate, and increased ATP production. However, PDK4 overexpression in HK-2 cells abolished the protective effects of GATM, enhanced glycolysis, increased lactate levels, and reduced ATP production.</p><p><strong>Conclusion: </strong>GATM plays a protective role in S-AKI by inhibiting PDK4-mediated aerobic glycolysis, enhancing ATP production, and restoring energy metabolism and mitochondrial function in PTCs.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863883","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":"Astrocyte-derived miR-124 impairs glioma cell volume regulation and migration by reducing Ca²⁺-dependent IK channel expression and activation.","authors":"Myriam Catalano, Arianna Rinaldi, Angela Di Battista, Cristina Limatola, Luigi Catacuzzeno, Antonio Michelucci","doi":"10.1007/s00018-026-06217-x","DOIUrl":"https://doi.org/10.1007/s00018-026-06217-x","url":null,"abstract":"<p><p>Astrocytes play a key role in regulating glioma cell volume, a major determinant of tumor invasiveness. We previously reported that astrocyte-derived extracellular vesicles (ADEVs) transfer microRNA miR-124 to murine glioma cells, impairing cell volume regulation and reducing the functional expression of volume-regulated anion channel (VRAC). Here, we identify the intermediate-conductance Ca²⁺-activated K⁺ (IK) channel, the only volume-regulated K⁺ channel acting in concert with VRAC in GL261 glioma cells, as an additional indirect target of miR-124. Mechanistically, ADEV-derived miR-124 decreases the expression of ryanodine receptor type-1 (RyR1) and inositol 1,4,5-trisphosphate receptor type-3 (IP₃R3), the principal endoplasmic reticulum (ER) Ca²⁺ release channels in these cells. This reduction in ER-mediated Ca²⁺ signaling markedly decreases ERK1/2 phosphorylation and IK channel gene transcription. Consistent with these molecular effects, fetal bovine serum-induced IK channel activation, driven by ER Ca²⁺ release, was strongly reduced by ADEVs and miR-124, and three-dimensional migration was impaired. Notably, combined pharmacological inhibition of IK and VRAC recapitulated the deficits in volume regulation induced by ADEVs and miR-124. Collectively, these findings show that ADEVs restrict glioma cell migration through a miR-124-dependent pathway that suppresses ER Ca²⁺ release, reduces ERK1/2 activation, and diminishes IK channel expression and function. Together with our previous in vivo evidence for ADEVs- and miR-124 -mediated targeting of VRAC, these results identify coordinated regulation of K⁺ and Cl⁻ channels as a mechanism by which astrocytes constrain glioma progression.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855929","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":"The multi-omics regulatory landscape of human early embryogenesis.","authors":"Yi-Wen Ding, Li-Quan Zhou, Ya-Xin Guo, Qiang Li","doi":"10.1007/s00018-026-06231-z","DOIUrl":"https://doi.org/10.1007/s00018-026-06231-z","url":null,"abstract":"<p><p>Human early embryonic development relies on a highly coordinated regulatory network, which establishes the molecular foundation for individual life. These early events are closely associated with assisted reproductive outcomes, embryo quality assessment, and the etiology of developmental disorders. Although studies in model organisms such as mice have elucidated several key regulatory mechanisms, research on human embryos has progressed relatively slowly due to long-standing challenges in sample acquisition and ethical constraints. In recent years, advances in single-cell omics and high-throughput technologies for ultra-low-input samples, combined with the appropriate utilization of clinically discarded embryos-including parthenogenetic (PG), androgenetic (AG), tripronuclear (3PN), and normal bipronuclear (2PN) embryos-have enabled the systematic profiling of the transcriptomics, epigenomics, proteomics, and metabolomics during human early embryogenesis. This review summarizes the developmental potential and molecular characteristics of different embryo types, synthesizes key multi-omics findings on the regulation of human embryogenesis, and untangles the complex cooperation and imbalance between parental genomes in shaping cell fate decisions. Furthermore, we compare species-specific and shared regulatory mechanisms between humans and mice, providing a conceptual framework for constructing more physiologically relevant models of human early development.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834365","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":"Correction: MiR‑17 and miR‑19 cooperatively promote skeletal muscle cell differentiation.","authors":"Delin Kong, Mei He, Lin Yang, Rongtao Zhou, Yun-Qin Yan, Yang Liang, Chun-Bo Teng","doi":"10.1007/s00018-026-06198-x","DOIUrl":"https://doi.org/10.1007/s00018-026-06198-x","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"83 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834435","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":"Small heat shock proteins and biomolecular condensates.","authors":"Samuele Crotti, Valentina Secco, Marialaura Morini, Serena Carra","doi":"10.1007/s00018-026-06216-y","DOIUrl":"https://doi.org/10.1007/s00018-026-06216-y","url":null,"abstract":"<p><p>Proteins comprise well-ordered structural domains and intrinsically disordered regions that explore broad conformational ensembles, a pervasive feature of the human proteome that underlies key aspects of cellular physiology. In the crowded intracellular environment, stress can shift protein conformational equilibria toward aggregation-prone states, exposing hydrophobic regions that can drive aberrant protein-protein interactions, promoting aggregation. To maintain proteome integrity, cells depend on an integrated protein‑quality‑control network in which molecular chaperones, their co‑factors and dedicated degradation systems act in concert. Within this network, small heat shock proteins serve as an ATP-independent first line of defense that stabilizes non-native proteins and limits irreversible aggregation. Recent work shows that small heat shock proteins can also safeguard the liquid‑like dynamics of biomolecular condensates formed by liquid-liquid phase separation. These membraneless compartments organize cellular biochemistry but are susceptible to stress- and disease-induced arrest or aggregation. Rather than undergoing phase separation autonomously, small heat shock proteins can be recruited into pre-existing condensates such as stress granules, nuclear speckles, p62 bodies, and condensates formed by disease-associated proteins, where they help preserve condensate fluidity. Together, these findings position small heat shock proteins as modulators of condensate dynamics that link protein quality control to mesoscale cellular organization, with important implications for cell biology, aging, and human disease.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811766","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":"Insulin production in the retina drives autocrine signalling and metabolism reprogramming of the ARPE-19, a retinal pigment epithelium cellular model.","authors":"Alessandra Puddu, Matilde Balbi, Silvia Ravera, Isabella Panfoli, Davide Maggi","doi":"10.1007/s00018-026-06222-0","DOIUrl":"https://doi.org/10.1007/s00018-026-06222-0","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) plays a pivotal role in retinal homeostasis and energy metabolism. A recent study demonstrates that RPE cells release insulin in response to photoreceptor outer segment (POS) phagocytosis and starvation conditions. However, the downstream signalling pathway of this local insulin production has not yet been identified. Therefore, using the ARPE-19 cell line as an in vitro model of human RPE, we have investigated insulin signalling in basal conditions and after rod OS phagocytosis. Our data show that ARPE-19 cells express key pancreatic β-cell markers, including the transcription factor Pancreatic and Duodenal Homeobox-1 (PDX-1), which translocates to the nucleus in response to phagocytosis, and prohormone convertase 1/3 (PC1/3). In addition, ARPE-19 cells synthesize and secrete insulin already in basal conditions, increasing their release after phagocytosis. The RPE-secreted insulin acts in an autocrine manner, activating the canonical insulin signalling pathway and leading to increased phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and AKT. An upregulation of the insulin-responsive glucose transporter GLUT4 and increased glucose uptake was also observed, fueling the ARPE-19 cells' oxidative energy metabolism, incrementing the oxidative phosphorylation activity, probably to sustain the high energy demand associated with phagocytosis. At the same time, a decrease in lactate release has been observed. These features may have important implications for understanding retinal energy metabolism and developing novel therapeutic strategies for retinal neurodegenerative diseases.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811800","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":"Sirtuin 7 ameliorates hypertensive intestinal injury by restoring epithelial barrier integrity and gut microbiota homeostasis.","authors":"Siyuan Wang, Minjie Wang, Xinyu Zhou, Kaixin Yan, Yufei Chen, Yihang Chen, Yaxuan Yao, Ying Dong, Jiuchang Zhong, Jing Li","doi":"10.1007/s00018-026-06229-7","DOIUrl":"https://doi.org/10.1007/s00018-026-06229-7","url":null,"abstract":"<p><p>Hypertension is increasingly recognized as a contributor to intestinal barrier disruption and gut microbiota dysbiosis, thereby promoting systemic inflammation and end-organ damage. Sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has been identified as a crucial regulator in the progression of cardiovascular diseases through multiple mechanistic pathways. However, the roles and underlying mechanisms of SIRT7 in the development of hypertensive intestinal injury remains unclear, and further investigation is required to determine whether SIRT7 can alleviate intestinal damage through modulation of the gut microbiota. In this study, SIRT7 expression and intestinal pathology were assessed in spontaneously hypertensive rats (SHRs). An intestinal SIRT7 overexpression model was subsequently established in SHRs to evaluate its effects on intestinal dysfunction and microbial composition. Histological and immunofluorescence staining were performed to examine the small intestine, and 16S rRNA amplicon sequencing was conducted to analyze the gut microbiota. There was a marked deficiency of SIRT7 in the intestinal tract of hypertensive animals, which was closely associated with reduced expression of tight junction proteins, including Occludin and zonula occludens-1, as well as intestinal pathological damage in SHRs. SIRT7 overexpression strikingly alleviated intestinal fibrosis, structural damage, and increased intestinal permeability. More importantly, restoration of SIRT7 partially reversed hypertension-associated gut microbiota dysbiosis. In summary, our findings provide novel mechanistic insights into the role of SIRT7 as a critical protector of intestinal barrier integrity and microenvironmental homeostasis under hypertensive stress, and highlight the intricate interplay between SIRT7 and the gut microbiota during hypertension.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811726","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":"Resident microbes shape host immunity and protect against pathogen infection and inflammatory disease.","authors":"Daichi Mori, Yoshiyuki Goto","doi":"10.1007/s00018-026-06219-9","DOIUrl":"https://doi.org/10.1007/s00018-026-06219-9","url":null,"abstract":"<p><p>The gastrointestinal tract harbors a vast and diverse community of microorganisms that establish a mutualistic and stable relationship with the host. These resident microbes play critical roles in protecting the host from luminal antigens, particularly pathogenic and opportunistic microorganisms, while simultaneously contributing to intestinal homeostasis. Accumulating evidence indicates that the gut microbiota profoundly shapes the development, differentiation, and function of epithelial and immune cells through coordinated molecular and cellular interactions. Recent studies have highlighted that barrier formation and immune homeostasis in the intestine are not solely host-driven processes but rather arise from cooperative interactions between resident microorganisms and host epithelial and immune compartments. Microbiota-derived signals promote epithelial integrity and instruct innate and adaptive immune responses, collectively establishing a robust yet tightly regulated infection-defense system that suppresses intestinal inflammation and maintains immune homeostasis. In this review, we focus on the role of the gut microbiota in the development of the host immune system, especially innate and adaptive lymphocytes, including epithelial cells, innate lymphoid cells, Th17 cells, and IgA⁺ B cells. We discuss how resident microorganisms shape these immune components to form a protective barrier system that not only confers resistance to pathogenic and opportunistic microbial infections but also maintains local and systemic immune homeostasis. Furthermore, we address how disruption of these microbiota-driven regulatory networks can contribute to the development of inflammatory diseases, highlighting the importance of host-microbiota interactions in health and disease.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763895","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":"Correction: TCF7L2 is essential for the differentiation and invasive function of human extravillous trophoblast.","authors":"Enoch Appiah Adu-Gyamfi, Joudi Salamah, Elisha Cheeran, Brandt Beck, Zaineb Ahmad, Bum-Kyu Lee","doi":"10.1007/s00018-026-06214-0","DOIUrl":"10.1007/s00018-026-06214-0","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"83 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763913","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":"Pregnancy-induced hypertension are preceded by prenatal perturbations of the gut microbiome and metabolome.","authors":"Huiyuan Pang, Bo Peng, Xin Yan, Jia Wang, Yixuan Lu, Xianxian Yuan, Yujie Zhang, Lirui Zhang, Junhua Huang, Ya Zhang, Ruihua Yang, Xu Ma, Xiaoxin Wang, Chenchen Fan, Li Zhang, Wei Song, Yumei Cheng, Shengnan Liang, Yuanyuan Wang, Wei Zheng, Guanghui Li","doi":"10.1007/s00018-026-06221-1","DOIUrl":"https://doi.org/10.1007/s00018-026-06221-1","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763928","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}