Journal of Cell Communication and Signaling最新文献

{"title":"Writing by proxy: Authentic authorship in the era of AI-powered communication of scientific knowledge","authors":"Brahim Chaqour","doi":"10.1002/ccs3.70120","DOIUrl":"https://doi.org/10.1002/ccs3.70120","url":null,"abstract":"<p>Artificial intelligence (AI) is reshaping biomedical research as both a key analytical tool and an efficient copyeditor. Large language models and related algorithms can help investigators sift through the ever-expanding bodies of scientific literature, connect fragmented biological and clinical datasets, and uncover/recognize meaningful patterns buried within complex multidimensional data. Beyond the bench, these tools can improve and refine manuscript architecture and streamline the flow of information by honing the articulation of simple or complex scientific ideas and sharpening the clarity and cadence of scientific information, which ultimately strengthens the writing in publications and grant proposals alike. For researchers working across languages or at early career stages, these tools allow them to express ideas with greater clarity and fluency, ultimately ensuring that intellectual contributions are assessed on the basis of their conceptual merit and experimental validity. However, the growing persuasiveness of AI-generated writing raises an important concern as to whether persuasive language can create an impression of rigor that is not necessarily matched by rigorous science. AI tools can improve the clarity and presentation of scientific writing, but they cannot establish biological relevance, experimental validation and/or the nuanced judgment required to identify confounding variables, and draw meaningful conclusions. Similarly, an eloquently written grant proposal cannot substitute for an innovative idea, testable hypothesis, feasible experimental approach, and meaningful anticipated contribution. It is therefore essential to view AI tools as instruments of improvement not replacement. They can enhance clarity, efficiency, and readability but they should not replace investigators' intellectual ownership, accountability, and critical interpretation. Disclosure of AI use, together with continued investigators' responsibility for originality, accuracy, citations, data integrity, and interpretation, is essential to maintain trust in scientific discoveries. Similarly, editors, peer reviewers, authors, and funding panels bear a renewed obligation to distinguish writing quality from scientific quality and continue to evaluate approach, innovation, experimental rigor, reproducibility, investigator skills, and scientific and/or clinical significance. Used judiciously and with discernment, AI can free researchers to invest more deeply in the irreplaceable human dimensions of scientific discovery.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205672","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":"Dermal fibroblasts cultured from aged human skin display a pro-inflammatory phenotype","authors":"Yilei Cui,&nbsp;Mai Shi,&nbsp;Christal Worthen,&nbsp;Sherilyn Grill,&nbsp;Jayakrishnan Nandakumar,&nbsp;Yi Zhao,&nbsp;Gary J. Fisher","doi":"10.1002/ccs3.70117","DOIUrl":"https://doi.org/10.1002/ccs3.70117","url":null,"abstract":"<p>Dermal fibroblasts synthesize, organize, and reside within the dermal extracellular matrix (ECM), which provides mechanical support to the skin and a microenvironment critical for dermal cell function. During aging, the ECM becomes fragmented, a change associated with clinical manifestations such as thin, fragile skin and altered fibroblast function, including reduced expression of ECM structural genes and increased expression of pro-inflammatory mediators. We investigated whether functional alterations of fibroblasts in aged skin reflect adaptation to the aged dermal ECM microenvironment or intrinsic aging responses. Primary dermal fibroblast cultures were established from young (20–30 years; 6 females, 6 males) and aged (&gt;80 years; 6 females, 6 males) sun-protected skin. No differences in early growth kinetics were observed between groups; however, fibroblasts from aged individuals grew more slowly after approximately 25 population doublings and had a 20% lower final population doubling level. Prior to passage, after brief primary culture (6–8 days), the average telomere length of fibroblasts from aged donors was reduced by approximately 1000 base pairs (∼1 kb). Global gene expression revealed 477 differentially expressed genes (DEGs; padj ≤0.05, absolute log2FC ≥ 0.58), comprising 300 upregulated and 177 downregulated transcripts. Upregulated DEGs and associated protein–protein interaction networks were enriched in cytokine- and chemokine-mediated signaling pathways (<i>p</i> &lt; 10⁻⁵). Downregulated DEGs were enriched in lipid biosynthesis and fatty acid metabolism. Notably, fibroblasts from young and aged skin expressed similar levels of genes encoding ECM structural proteins, including collagens (42 genes), proteoglycans (29 genes), and glycoproteins (157 genes). These findings indicate that fibroblasts from aged skin retain a pro-inflammatory transcriptional phenotype in primary culture, resembling their phenotype in vivo. In contrast, primary fibroblasts from aged skin express youthful levels of ECM structural genes in primary culture, suggesting that reduced ECM gene expression in vivo reflects dynamic adaptation to the aged dermal microenvironment rather than permanent reduction of synthetic capacity.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099335","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":"NRF2-CDH6-CEBPD axis suppresses ferroptosis and drives cisplatin resistance in non-small cell lung cancer","authors":"Guang-ze Zhou,&nbsp;Zhuo-hang Zhu,&nbsp;Hong-li Liao,&nbsp;Rui-heng Chen,&nbsp;Dan-ni Wu,&nbsp;Ri-sheng Huang","doi":"10.1002/ccs3.70115","DOIUrl":"10.1002/ccs3.70115","url":null,"abstract":"<p>Ferroptosis is a non-apoptotic form of programmed cell death driven by iron-dependent lipid peroxidation. Induction of ferroptosis has been shown to overcome chemoresistance in cancer cells. Given the importance of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in the regulation of cellular oxidative stress, this study was designed to search for NRF2-regulated genes involved in ferroptosis and chemoresistance in non-small cell lung cancer (NSCLC). Bioinformatics analysis and experimental validation indicated cadherin-6 (CDH6) as a candidate gene. The expression and role of CDH6 in NSCLC were explored. CDH6 protein partners were identified and investigated after CDH6 co-immunoprecipitation assays and mass spectrometry. Our data demonstrated that NRF2 binding to the promoter of the CDH6 gene inhibited RUNX2-mediated transcription of CDH6 in NSCLC. Clinically, CDH6 was downregulated in NSCLC tissues and correlated with more advanced tumor-node-metastasis (TNM) stage and shorter overall survival. Knockdown of CDH6 enhanced the proliferation, colony formation, tumorigenesis, and cisplatin (CDDP) resistance in NSCLC cells. Moreover, overexpression of CDH6 induced ferroptosis and increased CDDP sensitivity in CDDP-resistant NSCLC cells. Mechanistically, CDH6 associated with and sequestered CCAAT enhancer binding protein delta (CEBPD) protein in the cytoplasm and impaired the CEBPD-dependent transcription of target genes. Depletion of <i>CEBPD</i> increased CDDP sensitivity of CDH6-depleted NSCLC cells, whereas overexpression of CEBPD restored CDDP resistance in CDH6-overexpressing NSCLC cells. Additionally, CEBPD upregulation was associated with poor prognosis in NSCLC patients. In conclusion, our data underscore the critical role of the NRF2-CDH6-CEBPD axis in modulating CDDP sensitivity in NSCLC and offer a potential therapeutic target for improving chemotherapy.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038873","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":"Correction to “Targeting the PI3K/Akt/NF-κB axis: Cluster of differentiation 5-like-mediated immunometabolic regulation of macrophage polarization in abdominal aortic aneurysm”","authors":"","doi":"10.1002/ccs3.70113","DOIUrl":"10.1002/ccs3.70113","url":null,"abstract":"<p>Yi, Hemoren, Nan Liu, Zhengyang Wu, et al. 2025. “Targeting the PI3K/Akt/NF-κB Axis: Cluster of Differentiation 5-Like-Mediated Immunometabolic Regulation of Macrophage Polarization in Abdominal Aortic Aneurysm.” <i>Journal of Cell Communication and Signaling</i>: e70048. https://doi.org/10.1002/ccs3.70048.</p><p>In the originally published article, the authors identified an inconsistency in the presentation of the control group in Figure 2. The original results for the control group did not align with the statistical logic required by the experimental design. Upon verification, the authors confirmed that this arose from an incorrect application of the control group definition.</p><p>As described in the Methods section, the “control Ang II-untreated group” refers to the baseline control group without Ang II treatment. To ensure that the experimental groups and results are consistent in terms of statistical logic, the control group in Figure 2 has been corrected to represent the baseline state without Ang II intervention.</p><p>Additionally, Figures 3, 6, and 7 have been updated to correct typos in the figure labeling. The corrected Figures 2, 3, 6 and 7 are shown below.</p><p>The funding source has been corrected to “Health Science and Technology Capacity Improvement Project of Jilin Province (2022LC035).”</p><p>We apologize for these errors.</p><p></p><p></p><p></p><p></p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024936","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":"Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis","authors":"Xinyu Dong,&nbsp;Xuesong Hu,&nbsp;Qi Liu,&nbsp;Yuhao Dong,&nbsp;Yan Xuan,&nbsp;Muning Wang,&nbsp;Siyao Chang,&nbsp;Tianyi Lu,&nbsp;Zhiyang Han","doi":"10.1002/ccs3.70106","DOIUrl":"10.1002/ccs3.70106","url":null,"abstract":"&lt;p&gt;Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single-cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single-cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC-related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand-receptor expression patterns and ligand-associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single-cell-derived inflammatory and remodeling signatures were represented at the tissue-transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine-response, and stress-response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll-like receptor signaling, and inflammasome-associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+ synthetic VSMCs, KRT7+ VSMC-like cells, interferon-responsive VSMCs, pericyte-like mural cells, and osteogenic/modulated VSMCs. Pseudotime analysis showed a broad contractile-to-osteogenic/modulated transcriptional continuum accompanied by increased expression of remodeling-associated genes and selected inflammatory or remodeling-associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand-receptor and ligand-associated target gene expression patterns involving SPP1–CD44, TNF–TNFRSF1A, IL1B–IL1R1/IL1RAP, MIF–ACKR3, PDGFB–PDGFRB, and FN1–SDC1/ITGB1. In GSE28829, inflammatory macrophage-, osteogenic/modulated VSMC-, candidate ligand-receptor expression-, SPP1–CD44 candidate axis-, and NicheNet-prioritized target program-related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrati","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891724","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":"Mechanobiological feedback loops and quantitative decision thresholds in organ fibrosis: Translational principles for antifibrotic therapy","authors":"Amedeo Lonardo,&nbsp;Ralf Weiskirchen","doi":"10.1002/ccs3.70111","DOIUrl":"10.1002/ccs3.70111","url":null,"abstract":"<p>Multiorgan fibrosis is a complex, maladaptive response to chronic injury, where the extracellular matrix (ECM) shifts from serving merely as a structural framework to becoming an active, sustained contributor to disease progression. We propose a unifying mechanobiological framework in which chronic injury promotes fibroblast activation and ECM remodeling, whereas the stiffened and remodeled ECM feeds back through integrins, mechanosensitive ion channels, collagen receptors, and Hippo-YAP/TAZ signaling to sustain fibrogenesis. Regulation of this process is governed by bidirectional feedback between cellular signaling and the matrix's physical properties across organs such as the lung, heart, liver, and kidney. This narrative review article presents recent advances in understanding mechanisms of cell–cell and ECM communication, paratensile signaling, mechanical feedback loops, cellular crosstalk and secretomes, quantitative therapeutic thresholds, and translational strategies for tissue remodeling. These developments collectively offer promising insights for the development of novel pharmacological agents targeting mechanotransduction pathways, ECM normalization, and cell-specific sensitization. We further define quantitative thresholds as diagnostic, action, and response thresholds that may support clinical decisions such as referral, treatment initiation, therapeutic monitoring, and clinical-trial enrichment. Finally, we provide specific details regarding the treatment of liver fibrosis before concluding with research agenda.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873784","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":"Virtual single-cell perturbation and genetic causal inference reveal CSF1R-dependent immunometabolic communication in iron metabolism-associated osteoarthritis","authors":"Yue Zhou,&nbsp;Guohang Shen,&nbsp;Lijing Si,&nbsp;Kaiyong Wang,&nbsp;Yang Chen,&nbsp;Ruoyan Wang,&nbsp;Yupei Dai","doi":"10.1002/ccs3.70107","DOIUrl":"10.1002/ccs3.70107","url":null,"abstract":"<p>Iron dysregulation has emerged as a contributor to osteoarthritis (OA), yet the cell-communication mechanisms connecting iron-related genetic signals to joint degeneration remain insufficiently defined. Here, we established an integrative computational framework combining transcriptomic screening, machine learning, Mendelian randomization, immune and metabolite mediation analysis, single-cell transcriptomics, virtual gene perturbation, molecular docking, molecular dynamics simulation, and experimental validation to identify signaling regulators involved in iron metabolism-associated OA. By intersecting iron metabolism-related genes, OA differentially expressed genes, and eQTL-supported genes, we identified 27 shared candidates. Machine learning-based prioritization and genetic causal inference further highlighted <i>CSF1R</i> as a central regulatory gene. Single-cell analysis localized CSF1R expression predominantly to macrophages, indicating a macrophage-centered role in the osteoarthritic microenvironment. Mediation analysis integrating 731 immune-cell traits and 1400 circulating metabolites identified CD14⁺CD16⁺ monocytes as a significant cellular mediator linking <i>CSF1R</i> activity to OA susceptibility, suggesting that <i>CSF1R</i> may promote disease progression mainly through monocyte–macrophage remodeling rather than isolated metabolic alteration. Genetic colocalization further supported a shared regulatory signal between <i>CSF1R</i> expression and OA risk. Virtual single-cell perturbation revealed distinct downstream consequences of <i>CSF1R</i> modulation. Simulated <i>CSF1R</i> depletion enhanced antigen processing, major histocompatibility complex class II presentation, and phagosome-related programs, whereas simulated <i>CSF1R</i> overexpression preferentially activated extracellular matrix organization, integrin signaling, and cartilage development-associated pathways. Structural analyses identified stable interactions between <i>CSF1R</i> and candidate inhibitory compounds, and inflammatory stimulation of macrophages confirmed increased <i>CSF1R</i> protein expression. Collectively, this study identifies <i>CSF1R</i> as a macrophage-associated immunometabolic signaling hub linking iron dysregulation to OA. These findings provide a mechanistic basis for targeting <i>CSF1R</i>-mediated monocyte–macrophage communication and offer a computational strategy for prioritizing therapeutic targets in degenerative joint disease.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840245","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":"Extracellular high mobility group box 1 as a UV-induced alarmin driving cutaneous inflammation and photoaging via TLR4 signaling","authors":"Qian Liufu,&nbsp;Zhaoping Qin,&nbsp;Yan Yan,&nbsp;Yiru Xu,&nbsp;Tianyuan He,&nbsp;Yingchun Liu,&nbsp;Yaping Xiang,&nbsp;Chunfang Guo,&nbsp;Taihao Quan","doi":"10.1002/ccs3.70109","DOIUrl":"https://doi.org/10.1002/ccs3.70109","url":null,"abstract":"<p>High mobility group box 1 (HMGB1) is a nuclear protein that functions as a damage-associated molecular pattern molecule upon extracellular release. It has an established role in sterile inflammation, yet its involvement in UV-induced human skin inflammation remains poorly characterized. This study investigated whether UV irradiation and chronic photoaging trigger HMGB1 release in human skin and whether this release drives proinflammatory cytokine expression and photoaging. Both acutely UV-irradiated and chronically photoaged human skin exhibited HMGB1 release, which temporally correlated with the upregulation of photoaging-related critical proinflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α. In cultured cells, UV irradiation reduced intracellular HMGB1 protein without altering mRNA levels while simultaneously increasing extracellular HMGB1 in supernatants, confirming active secretion rather than passive leakage. HMGB1 knockdown and blockade of TLR4, its principal receptor, significantly attenuated UV-induced proinflammatory cytokine expression in both cell types. In mouse skin, disruption of the HMGB1–TLR4 axis reduced neutrophil infiltration, suppressed cytokine expression, and mitigated dermal damage (photoaging). Collectively, these findings demonstrate that UV irradiation promotes active HMGB1 release from skin cells, amplifying cutaneous inflammation and exacerbating dermal damage via TLR4 signaling. Therapeutic targeting of the HMGB1–TLR4 axis therefore represents a promising strategy for mitigating UV-induced skin inflammation and its downstream pathologies, including photoaging.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ccs3.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849105","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":"Critical role of cellular communication network factor 1 in early osteogenesis of mesenchymal stem cells primed by low-intensity pulsed ultrasound and bone morphogenetic protein 2","authors":"Hsu Myat Paing,&nbsp;Satoshi Kubota,&nbsp;Masaharu Takigawa,&nbsp;Takuo Kuboki,&nbsp;Takashi Nishida","doi":"10.1002/ccs3.70101","DOIUrl":"10.1002/ccs3.70101","url":null,"abstract":"<p>There is a known reciprocal inhibitory relationship between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs). Our previous study showed that low-intensity pulsed ultrasound (LIPUS) did not promote osteogenesis of a murine MSC line C3H10T1/2, although LIPUS treatment suppressed adipogenesis. Therefore, we investigated the effect of a combination of an osteoinductive factor such as bone morphogenic protein-2 (BMP-2) and LIPUS treatment on osteogenesis. This combination significantly upregulated the gene expressions of BMP receptors and RUNX2, which is a key early osteogenic transcription factor. Interestingly, cellular communication network factor 1 (CCN1) was significantly increased at the mRNA and protein levels. Additionally, <i>Runx2</i> expression was increased by a recombinant CCN1 protein and decreased in CRISPR-Cas9-generated <i>Ccn1</i> knockout (KO) cells treated with the combination of LIPUS treatment and BMP-2. Moreover, <i>Runx2</i> expression was recovered through the transfection of a <i>Ccn1</i> expression plasmid into <i>Ccn1</i> KO cells. These findings indicate that treatment with the combination of LIPUS treatment and BMP-2 promoted CCN1 production, and the CCN1 regulates the <i>Runx2</i> expression in C3H10T1/2 cells, thus suggesting that CCN1 induced by mechanical stimulation and an osteoinductive factor plays a pivotal role in osteogenesis of MSCs.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13513212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828634","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":"FOXO6 inhibits SMURF2-mediated ubiquitination and degradation of NR4A1 to promote retinal pigment epithelial cell ferroptosis in diabetic retinopathy","authors":"Qiao Chen,&nbsp;Bo Su,&nbsp;Ke Xu,&nbsp;Liang Li,&nbsp;Changzheng Chen","doi":"10.1002/ccs3.70108","DOIUrl":"10.1002/ccs3.70108","url":null,"abstract":"<p>Diabetic retinopathy (DR) is the main cause of vision loss, with retinal pigment epithelial (RPE) cell dysfunction as a key contributor. Ferroptosis is implicated in RPE injury under hyperglycemia; however, its upstream regulatory mechanisms remain unclear. High glucose (HG)-induced human RPE ARPE-19 cells and a diabetic mouse model were used. Ferroptosis was assessed through biochemical assays, Western blot, fluorescence probes, and histological staining. Protein interactions and transcriptional regulation were examined using Co-IP, glutathione S-transferase pull-down, ChIP, and luciferase reporter assays. Immunofluorescence staining was used as key indicator expression in retinal tissues. Nuclear receptor 4A1 (NR4A1) expression was upregulated under HG-induced ARPE-19 cells. NR4A1 knockdown alleviated HG-induced iron accumulation, lipid peroxidation, and ferroptosis marker changes. Mechanistically, SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) interacted with NR4A1 and promoted its ubiquitination and degradation. Forkhead box O6 (FOXO6) was upregulated by HG and repressed SMURF2 transcription. SMURF2 overexpression mitigated HG-induced ARPE-19 ferroptosis and retinal injury in DR mice, an effect reversed by NR4A1 co-overexpression. SMURF2 knockdown reversed the effect of FOXO6 knockdown on HG-induced ferroptosis in ARPE-19 cells and retinal injury in DR mice. The FOXO6–SMURF2–NR4A1 axis critically regulates ferroptosis in RPE cells during DR.</p>","PeriodicalId":15226,"journal":{"name":"Journal of Cell Communication and Signaling","volume":"20 3","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828627","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}