Journal of Cell Communication and Signaling最新文献

{"title":"Inflammatory cytokine IL-6 regulates ADAMTS14 expression through MAPK and PI3K signaling in colorectal cancer","authors":"Nelin Hacioglu,&nbsp;Rümeysa Nur Vapur Ondul,&nbsp;Ghufran Haqi Ismael,&nbsp;Feray Kockar","doi":"10.1002/ccs3.70092","DOIUrl":"https://doi.org/10.1002/ccs3.70092","url":null,"abstract":"<p>Extracellular matrix (ECM) remodeling is a critical component of colorectal cancer (CRC) progression and tumor microenvironment organization. Members of the A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) metalloproteinase family are known regulators of ECM structure; however, the transcriptional regulation of ADAMTS14 and its potential role in inflammation-associated ECM remodeling remain poorly understood. In this study, we investigated whether inflammatory signaling regulates ADAMTS14 expression and explored its association with ECM organization in CRC. Interleukin-6 (IL-6) stimulation significantly increased ADAMTS14 expression at both mRNA and protein levels in CRC cells. Promoter deletion analyses identified a critical IL-6-responsive region between −145 and −43 bp upstream of the transcription start site, suggesting transcriptional responsiveness of ADAMTS14 to inflammatory signaling. Inhibition experiments demonstrated that Extracellular Signal-Regulated Kinase, c-Jun N-terminal Kinase, Phosphatidylinositol 3-Kinase, and Nuclear Factor Kappa B pathways were associated with IL-6-induced ADAMTS14 expression. Transcriptomic analyses of The Cancer Genome Atlas CRC datasets revealed that ADAMTS14 expression is elevated in tumors and is associated with inflammatory signaling, stromal activation, fibroblast-related gene expression, and ECM organization pathways. Functional enrichment analyses indicated that ADAMTS14-correlated genes are primarily involved in ECM organization, collagen fibril organization, and connective tissue development. Together, these findings identify ADAMTS14 as an inflammation-responsive ECM-associated metalloproteinase and suggest that IL-6 signaling may be associated with ECM-related transcriptional programs through regulation of ADAMTS14 expression. Our findings further suggest that ADAMTS14 expression may be associated with inflammatory and stromal-related transcriptional programs in CRC.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gemcitabine activates the Hippo signaling pathway and suppresses tumor growth by stabilizing large tumor suppressor kinase 2 through the hypoxia-inducible factor 1-alpha/ubiquitin protein ligase E3 component N-recognin 5 axis","authors":"Jin Zhang,&nbsp;Lixia Xu,&nbsp;Kai Guo,&nbsp;Weijia Dong,&nbsp;Xin Dai,&nbsp;Donghua Gu","doi":"10.1002/ccs3.70085","DOIUrl":"10.1002/ccs3.70085","url":null,"abstract":"<p>To investigate the molecular mechanism by which gemcitabine (GEM) inhibits ovarian cancer (OC) progression, focusing on the hypoxia-inducible factor 1-alpha (HIF1A)/UBR5/LATS2 axis and Hippo pathway. Bioinformatics analysis of gene expression omnibus datasets identified HIF1A-associated modules. Transcriptional regulation of UBR5 by HIF1A was validated via ChIP-PCR and dual-luciferase assays. Anti-tumor effects of GEM were assessed in OC cell lines and an orthotopic mouse model using functional assays (CCK-8, transwell), Western blot, Co-IP, and ubiquitination analysis. HIF1A transcriptionally upregulates UBR5 in OC. GEM downregulated the HIF1A/UBR5 axis, suppressing OC cell proliferation, migration, and invasion. Mechanistically, UBR5 promoted LATS2 ubiquitination and degradation. GEM inhibited this interaction, stabilizing LATS2, activating the Hippo pathway, and suppressing downstream YAP1/FGFR1 signaling. In vivo, GEM inhibited tumor growth and downregulated HIF1A, UBR5, and FGFR1. GEM suppresses OC progression by targeting the HIF1A/UBR5 axis, which subsequently stabilizes LATS2, activates the Hippo pathway, and inhibits YAP1/FGFR1 signaling, revealing a novel therapeutic mechanism.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRMT10C promotes mitochondrial fission through transferrin receptor m1A methylation modification and aggravates the progression of atrial fibrillation","authors":"Nijina Li,&nbsp;Hao Zhang","doi":"10.1002/ccs3.70059","DOIUrl":"10.1002/ccs3.70059","url":null,"abstract":"<p>Atrial fibrillation (AF) is a common cardiac arrhythmia often accompanied by structural remodeling of the atria, particularly fibrosis, and disruption of normal mitochondrial function. N(1)-methyladenosine (m1A), a methylation of RNA, is gaining attention for its role in diverse biological processes. This study aimed to explore the role of the m1A methyltransferase tRNA methyltransferase 10C (TRMT10C) in AF pathogenesis. In the study, TRMT10C and m1A methylation levels were upregulated in AF rats, accompanied by excessive mitochondrial fission and myocardial fibrosis. Knockdown of TRMT10C inhibited the expression levels of mitochondrial fission-related proteins Drp1 and Fis1, reduced collagen deposition (collagen I, Postn, collagen III, and fibronectin), and AF progression. In vitro results showed that TRMT10C knockdown inhibited TGF-β1-induced cardiac fibroblasts proliferation and migration, whereas overexpression of transferrin receptor (TFRC) reversed this effect. Mechanistically, TRMT10C enhanced the stability of TFRC mRNA by promoting m1A methylation, driving mitochondrial fission and fibrosis. Collectively, our findings elucidate a novel TRMT10C–TFRC m¹A axis driving pathological mitochondrial dynamics and fibrosis in AF, offering new insight into cell-signaling pathways underlying atrial disease and potential therapeutic targets.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis identifies a major histocompatibility complex class II-associated antigen-presenting cancer-associated fibroblast-like state linked to the nuclear factor erythroid 2-related factor 2-karyopherin subunit beta 1 axis in nonsmall cell lung cancer","authors":"Fei Zheng,&nbsp;Ruoying Deng,&nbsp;Ran Hou,&nbsp;Lei Hong,&nbsp;Yanzhi Cui,&nbsp;Yibing Liu","doi":"10.1002/ccs3.70074","DOIUrl":"https://doi.org/10.1002/ccs3.70074","url":null,"abstract":"<p>To define the transcriptional features, spatial distribution, and immune-related properties of an antigen-presenting cancer-associated fibroblast (CAF)-like state in nonsmall cell lung cancer (NSCLC), and to evaluate its relationship with the nuclear factor erythroid 2-related factor 2 (NRF2)-karyopherin subunit beta 1 (KPNB1) axis, multi-omics analyses integrating single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic data were performed. Functional validation used primary CAFs from patients with NSCLC, including NRF2 perturbation, KPNB1 knockdown, T-cell co-culture assays, and an orthotopic murine lung cancer model treated with antiprogrammed cell death protein 1 (anti-PD-1)-based combinations. A major histocompatibility complex class II (MHC-II)-associated antigen-presenting CAF-like (apCAF-like) state was identified in NSCLC. It showed increased antigen-presentation-related molecules, limited co-stimulatory molecule expression, and inferred communication involving MHC-II, transforming growth factor-β, and C-X-C motif chemokine ligand pathways. Higher KPNB1 expression was associated with poorer survival, lower immune infiltration, and lower ImmuneScore. In primary CAFs, NRF2 activation increased KPNB1 and reduced class II MHC transactivator, major histocompatibility complex class II DR alpha (HLA-DRA), and MHC-II-related signals, whereas NRF2 inhibition showed the opposite pattern. KPNB1-low CAFs enhanced T-cell activation and cytokine release, and KPNB1 knockdown enriched antigen-presentation-related transcriptional programs. In vivo, inhibition of the NRF2-KPNB1 axis enhanced response to anti-PD-1. NSCLC contains an MHC-II-associated apCAF-like state linked to the NRF2-KPNB1 axis and altered response to PD-1 blockade.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT1: Protean roles at the nexus of health, disease, and therapeutics","authors":"Brahim Chaqour","doi":"10.1002/ccs3.70086","DOIUrl":"https://doi.org/10.1002/ccs3.70086","url":null,"abstract":"<p>Silent mating type information regulators (sirtuins and SIRTs) have emerged as central nodes linking cellular metabolism to stress adaptation and diseases. SIRT1 stands out as a ubiquitously expressed, NAD⁺-dependent deacetylase with remarkably broad and sometimes paradoxical functions. Beyond its canonical roles in chromatin regulation and DNA repair, SIRT1 regulates key pathways controlling metabolism, inflammation, circadian rhythms, mitochondrial biogenesis, mitophagy, immune response, and cellular survival. Growing evidence, including several studies published in JCCS, positions SIRT1 at the intersection of cardiovascular, metabolic, neurovascular, and oncogenic processes, highlighting both its biological complexity and therapeutic potential. Mechanistically, SIRT1 modulates through deacetylation, a diverse network of substrates including histones H3/H4, tubulin, BMAL1, p53, NF-κB, FOXO, PGC-1α, and eNOS, yet, its functional outcomes are highly context dependent. Although SIRT1 activation is often protective in metabolic and cardiovascular and neurovascular settings, its role in cancer remains dualistic, acting as both tumor suppressor and promoter. Similarly, its contribution to longevity remains unresolved, with conflicting results across experimental models. Pharmacological targeting of SIRT1, through compounds such as resveratrol and synthetic modulators, has generated considerable enthusiasm, but challenges related to specificity, bioavailability, and off-target effects persist. Here, I discuss SIRT1 not simply as a therapeutic target but as a molecular “shapeshifter,” whose context-dependent actions demand more precise biomarker-guided strategies for clinical translation.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species-specific roles of cellular communication network proteins in cartilage development: A comparative study using in vitro chondrogenic models","authors":"Zhangzheng Wang,&nbsp;Judit Vágó,&nbsp;Roland Takács,&nbsp;Szilárd Póliska,&nbsp;Ee Hyun Kim,&nbsp;Eun-Jung Jin,&nbsp;Satoshi Kubota,&nbsp;Celina G Kleer,&nbsp;Bernard Perbal,&nbsp;Csaba Matta","doi":"10.1002/ccs3.70089","DOIUrl":"https://doi.org/10.1002/ccs3.70089","url":null,"abstract":"<p>Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species-specific roles and network-level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co-expression, protein–protein interaction, and ortholog analyses to construct CCN-centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen-containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context-dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF-1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species-specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including <i>COL2A1</i>, <i>TGFBR1</i>, <i>SMAD3</i>, <i>RUNX2</i>, <i>HIF1A</i>, <i>IGF1</i>, <i>SPP1</i>, and <i>CD44</i>. Single-cell RNA-seq meta-analysis of human iPSC-derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model-dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2-centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN-targeted cartilage regeneration strategies.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of diagnostic biomarkers for neonatal necrotizing enterocolitis via machine learning screening and single-cell virtual gene knockout validation","authors":"Xue Liu,&nbsp;Wenqiang Sun,&nbsp;Zengxue Hu,&nbsp;Yihui Li,&nbsp;Jingtao Bian,&nbsp;Xueping Zhu","doi":"10.1002/ccs3.70081","DOIUrl":"https://doi.org/10.1002/ccs3.70081","url":null,"abstract":"&lt;p&gt;Neonatal necrotizing enterocolitis (NEC) continues to be the most severe gastrointestinal emergency affecting preterm infants, with reported mortality rates ranging from 20% to 30%. The absence of distinct early biomarkers results in delayed intervention and unfavorable outcomes, and the molecular mechanisms underlying the dysregulated immune response in NEC remain incompletely defined. We integrated five gene expression omnibus datasets (36 NEC cases and 34 controls) using weighted gene co-expression network analysis and systematically evaluated 113 machine learning algorithm combinations. The best-performing model (RF + XGBoost) identified candidate diagnostic genes, which were validated through independent bulk RNA-sequencing cohorts, single-cell RNA sequencing (11,308 intestinal cells), single-cell virtual gene knockout (scTenifoldKnk), and experimental models including mice and the intestinal epithelial cells cell line. Combinatorial in silico perturbation was further performed using Geneformer, and a ferroptosis gene panel was validated by qRT-polymerase chain reaction in the mouse NEC model. The RF + XGBoost model achieved high diagnostic accuracy (area under the curve = 0.979, 95% CI: 0.940–1.000). Three key biomarkers were identified: SLC26A3, CCL20, and CXCL5. Multi-platform validation showed consistent downregulation of SLC26A3 and upregulation of CCL20 and CXCL5 in NEC (all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Single-cell analyses revealed cell-type-specific dysregulation, with CCL20 markedly elevated in macrophages (log2FC = 3.85) and CXCL5 broadly upregulated across enterocytes, macrophages, and fibroblasts. Immune profiling demonstrated elevated proportions of M0 macrophages and activated mast cells, alongside reduced naive B cells and naive CD4 T cells, and CXCL5 expression was strongly correlated with neutrophil infiltration (&lt;i&gt;r&lt;/i&gt; = 0.88, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Virtual knockout analysis revealed that perturbation of CCL20 and CXCL5 produced overlapping downstream networks converging on major histocompatibility complex class II–related antigen presentation genes, whereas SLC26A3 knockout perturbed a distinct set of epithelial barrier and innate immune genes. FTH1 was the sole gene perturbed across all three knockouts, implicating ferroptosis as a potential convergence point in NEC pathogenesis. Geneformer-based combinatorial perturbation indicated subadditive rather than synergistic interactions among the three biomarkers, with SLC26A3 appearing as the dominant node. Extension to a 9-gene ferroptosis panel showed coordinated directional shifts across the tested genes, and qPCR measurements in the NEC mouse ileum were consistent with the predicted expression changes for the five measured genes. SLC26A3, CCL20, and CXCL5 constitute a candidate molecular signature for early NEC diagnosis. Combinatorial perturbation analysis suggests subadditive rather than synergistic interactions among the three biomarkers, with SLC26A3 appearing as the domi","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D receptor signaling in inflammatory senescence-associated skin aging: Mechanisms and therapeutic potentials.","authors":"Liancheng Guan, Fan Yang, Meijuan Li, Yujia Chen, Zexin Zhao, Hongxia Li, Deping Luo, Qian Li, Yunzhi Chen","doi":"10.1002/ccs3.70088","DOIUrl":"10.1002/ccs3.70088","url":null,"abstract":"<p><p>Vitamin D receptor (VDR) signaling plays a crucial role in skin homeostasis and represents a promising therapeutic target for inflammatory senescence-associated skin aging. This review examines the roles of VDR signaling in inflammatory senescence-associated skin aging. We summarize the actions of VDR through chromatin modification, transcriptional regulation, and coregulator recruitment, which collectively modulate inflammation and cellular senescence in aging skin. Recent findings highlight the protective role of VDR against inflammatory responses and aging processes through multiple pathways, including NF-κB suppression and regulation of senescence-associated pathways. The review discusses cell-type specific VDR regulation in keratinocytes, immune cells, dermal fibroblasts, and stem cells, emphasizing their distinct roles in skin homeostasis. Current therapeutic approaches encompass vitamin D-based treatments, traditional medicine-derived bioactive compounds, and novel drug delivery systems. Research challenges include limitations in monitoring VDR activity in aging skin and developing effective tissue-specific delivery methods. This analysis emphasizes the therapeutic potential of VDR modulation in aging-related skin conditions and highlights priorities for future investigation of VDR-mediated regulation in inflammatory senescence-associated skin diseases.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":"e70088"},"PeriodicalIF":4.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MIR503HG serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction.","authors":"Pingping Qi, Minghe Jiang, Minsheng Wu, Shengkui Chen, Qile Ye, Rong Tang","doi":"10.1002/ccs3.70078","DOIUrl":"10.1002/ccs3.70078","url":null,"abstract":"<p><p>Sepsis often has a dysregulated inflammatory response and is accompanied by cardiac dysfunction. This study aimed to explore the mechanism of long non-coding RNA MIR503HG (MIR503HG) in regulating sepsis and the inflammatory responses, and sepsis-induced cardiac dysfunction (SICD). 102 sepsis patients were divided into an SICD group (<i>n</i> = 31) and a non-SICD group (<i>n</i> = 71). A cecal ligation and puncture (CLP) sepsis rat model was constructed. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the target gene expression. Enzyme-linked immunosorbent assay was used to measure the levels of myocardial damage markers and inflammatory factors. RNA immunoprecipitation and Dual luciferase assay were used to determine the targeting relationship. Kyoto Encyclopedia of Genes and Genomes analysis was used to predict signaling pathways of target genes. MIR503HG expression was significantly down-regulated in sepsis patients and SICD patients, and it has good diagnostic value for these two types of diseases. Its expression was significantly negatively correlated with myocardial injury markers (cardiac troponin I [cTnI], creatine kinase-MB [CK-MB]), cardiac function indicators (left ventricular ejection fraction), inflammatory factors (interleukin-6, tumor necrosis factor-alpha), and disease severity scores (Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II). Furthermore, it exerted a protective effect in sepsis: MIR503HG overexpression could effectively alleviate SICD and mitigate the inflammatory response, as evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure, reduced levels of CK-MB and cTnI, as well as restored myocardial systolic/diastolic capacity (maximal rate of left ventricular pressure rise/fall [±dP/dt]). Mechanistically, MIR503HG functions as a molecular sponge that sequesters microRNA-497-5p (miR-497-5p), thereby lifting brain-derived neurotrophic factor (BDNF). Delivery of miR-497-5p-agomiR partially offset the cardioprotective and anti-inflammatory effects of MIR503HG, whereas overexpression of BDNF partially restored them. MIR503HG relieved sepsis and reduced cardiac dysfunction and inflammatory response by regulating the miR-497-5p/BDNF axis.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 2","pages":"e70078"},"PeriodicalIF":4.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}