FASEB bioAdvances最新文献

{"title":"Prognostic Value of TBC1D1 and Its Relationship With the Tumor Microenvironment in Pancreatic Cancer: A Study Based on Single-Cell Sequencing","authors":"Linfeng Yang,&nbsp;Duan Yan,&nbsp;Jun Yu,&nbsp;Dawei Deng,&nbsp;Lin Ma,&nbsp;Ruixin Yu,&nbsp;Song Wei,&nbsp;Jiahui Yu,&nbsp;Chuan Lan,&nbsp;Pengsheng Yi","doi":"10.1096/fba.2025-00092","DOIUrl":"https://doi.org/10.1096/fba.2025-00092","url":null,"abstract":"<p>TBC1 Domain Family Member 1 (TBC1D1) plays a crucial role in various cancers. However, its specific function in pancreatic cancer (PC) remains poorly understood. In this study, we aimed to evaluate the prognostic value of TBC1D1 and its correlation with the tumor microenvironment (TME) in PC. A total of 168 patients with PC were included in this study. The expression of TBC1D1 in patients was detected by immunohistochemistry. Additionally, single-cell RNA sequencing (scRNA-seq) was used to reveal the expression distribution and proportion of TBC1D1 across different cell populations. The relationship between TBC1D1 expression levels and the TME was further explored based on high and low TBC1D1 expression groups. Multivariate analysis revealed that TBC1D1 positivity was an independent adverse prognostic factor for overall survival (OS; <i>p</i> = 0.026). Immunohistochemistry and single-cell RNA sequencing analyses revealed that TBC1D1 expression was positively correlated with fibroblast activation protein, programmed cell death protein 1, and programmed cell death ligand-1 positivity but negatively correlated with clusters of differentiation 8T cells positivity. Our findings revealed that TBC1D1 is an independent prognostic risk factor in patients with PC and may promote PC progression by modulating the TME.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Human Early Embryonic Development","authors":"Jiwei Chen,&nbsp;Gaigai Wei,&nbsp;Fangge Sun,&nbsp;Yunjin Li,&nbsp;Shuang Tang,&nbsp;Geng Chen","doi":"10.1096/fba.2025-00075","DOIUrl":"https://doi.org/10.1096/fba.2025-00075","url":null,"abstract":"<p>Single-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression, but few scRNA-seq technologies were used to describe the expression dynamics at the isoform and exon levels. Although the current expression profile of early embryos was studied focusing on the expression changes at the gene level, systematic investigation of gene expression dynamics of human early embryonic development remains insufficient. Here we systematically explored the gene expression dynamics of human early embryonic development integrating gene expression level with alternative splicing, isoform switching, and expression regulatory network. We found that the genes involved in significant changes in these three aspects are all gradually decreased along embryonic development from E3 to E7 stage. Moreover, these three types of variations are complementary for profiling expression dynamics, and they vary significantly across embryonic development as well as between different sexes. Strikingly, only a small number of genes exhibited prominent expression level changes between male and female embryos in the E3 stage, whereas many more genes showed variations in alternative splicing and major isoform switching. Additionally, we identified functionally important specific gene regulatory modules for each stage and revealed dynamic usage of transcription factor binding motifs (TFBMs). In conclusion, this study provides informative insights into gene dynamic characteristics of human early embryonic development by integrating gene expression level with alternative splicing, isoform switching, and gene regulatory networks. A systematic understanding of gene dynamic alteration features during embryonic development not only expands knowledge on basic developmental biology but also provides fundamental insights for regenerative medicine and developmental diseases.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prothrombotic Biomarkers Are Not Altered by Wood Smoke: A Pilot Controlled Exposure Study","authors":"Dre' Von A. Dobson,&nbsp;Lori A. Holle,&nbsp;Kohei Tatsumi,&nbsp;Meghan E. Rebuli,&nbsp;Nigel Mackman,&nbsp;Alisa S. Wolberg,&nbsp;Ilona Jaspers","doi":"10.1096/fba.2025-00125","DOIUrl":"https://doi.org/10.1096/fba.2025-00125","url":null,"abstract":"<p>Inhalation of wood smoke (WS) has been associated with increased risk of cardiovascular events, including heart attacks and strokes, both of which are caused in part by the thrombotic occlusion of blood vessels. To characterize the effects of WS on levels of established, circulating prothrombotic biomarkers, healthy human subjects at rest were exposed to WS (500 μg/m³) or filtered air for 2 h. Plasma samples were then used to assess markers of endogenous procoagulant activity: cellular activation (tissue factor-positive extracellular vesicles, TF + EVs), thrombin-antithrombin complexes (TAT), fibrin formation/breakdown (D-dimer), and thrombin generation potential. No significant differences in TF + EVs, TATs, D-dimer, or thrombin generation parameters were detected between WS- or filtered air-exposed individuals. Although females had significantly higher TATs and D-dimers, and slightly but non-significantly shorter thrombin generation lag times than males, there were no significant differences between WS- or air-exposed males or females in any measurements. These data suggest that acute WS exposure does not increase prothrombotic biomarkers in plasma.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral MIB-626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With COVID-19 and Acute Kidney Injury: A Randomized Controlled Trial","authors":"Karol M. Pencina,&nbsp;David E. Leaf,&nbsp;Rodrigo J. Valderrabano,&nbsp;Sushrut S. Waikar,&nbsp;Tapan S. Mehta,&nbsp;Yili Valentine Shang,&nbsp;Nancy K. Latham,&nbsp;Tejossy John,&nbsp;Elena Volpi,&nbsp;Dahlene Fusco,&nbsp;Yusnie Memish-Beleva,&nbsp;Shobana Krishnamurthy,&nbsp;Siva Lavu,&nbsp;Salma Karmi,&nbsp;David J. Livingston,&nbsp;Shalender Bhasin","doi":"10.1096/fba.2025-00014","DOIUrl":"https://doi.org/10.1096/fba.2025-00014","url":null,"abstract":"<p>Nicotinamide adenine dinucleotide (NAD⁺) plays an important role in the innate immune response and is depleted during SARS-CoV-2 infection due to increased turnover. It is unknown whether treatment with NAD⁺ precursors can safely raise NAD⁺ levels in patients with COVID-19. To determine whether MIB-626 (<i>β-</i>nicotinamide mononucleotide), an NAD⁺ precursor, can safely increase blood NAD⁺ levels and attenuate acute kidney injury (AKI) and inflammation in hospitalized patients with COVID-19, 42 adults, ≥ 18 years, hospitalized with COVID-19 and AKI, were randomized in a 3:2 ratio to MIB-626 1.0-g or placebo tablets twice daily for 14 days. Circulating NAD⁺ and its metabolites, markers of AKI, inflammation, and disease severity, were assessed. MIB-626 treatment significantly but gradually raised blood NAD⁺ levels to a peak between 5 to 14 days (16.0 ± 6.9, 25.5 ± 12.6, and 42.6 ± 25.6 μg/mL at baseline, days 5 and 14) and raised plasma concentrations of NAD⁺ metabolites 1-methylnicotinamide, N-methyl, 2-pyridone, 4-carboxamide rapidly to a peak by day 3. Changes in serum creatinine, cystatin-C, and serum markers of AKI did not differ significantly between groups. Serum CRP, IL-6, and TNFα and indices of disease severity also did not differ between groups. MIB-626 treatment of patients with COVID-19 and AKI safely and substantially raised blood NAD⁺ and plasma concentrations of NAD⁺ metabolites. Markers of AKI, inflammation, and disease severity did not differ between groups, likely due to the slow rise in NAD⁺ levels. Future studies should assess whether a rapid increase in NAD⁺ by parenteral administration can attenuate disease severity and AKI.</p><p><b>Trial Registration:</b> ClinicalTrials.gov Identifier: NCT05038488</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Iron Supplementation Protects Against Growth Restriction and Metabolic Dysfunction-Associated Steatotic Liver Disease in Perinatal Cadmium-Exposed Mice","authors":"Rebecca Lichtler,&nbsp;Hannah Klossner,&nbsp;Nikia Smith,&nbsp;Cathrine Hoyo,&nbsp;Michael Cowley","doi":"10.1096/fba.2025-00045","DOIUrl":"https://doi.org/10.1096/fba.2025-00045","url":null,"abstract":"<p>Iron (Fe)-deficiency (ID) and Fe-deficiency anemia (IDA) are highly prevalent conditions and are of particular concern to maternal–child health. ID and IDA are typically linked to nutritional deficiencies, but maternal exposure to heavy metals including cadmium (Cd) also leads to offspring with low levels of circulating Fe. Another comorbidity of ID and IDA is metabolic dysfunction-associated steatotic liver disease (MASLD), a liver condition characterized by lipid accumulation and fibrosis. We have previously shown that maternal Cd exposure also leads to the development of MASLD in offspring. We hypothesized that providing Fe fortification would prevent Cd-induced ID, which would in turn rescue offspring from growth restriction and MASLD. To test this, virgin dams were exposed to 30 ppm of cadmium chloride (CdCl₂) in their drinking water during the preconception, gestation, and lactation periods. Fe fortification was supplied in the form of dietary ferric citrate, which amounted to two (2×) or five times (5×) the normal dietary Fe in standard chow. Our study provides evidence that perinatal Cd exposure does not prevent absorption of supplemental Fe, and that the chosen Fe supplementation dosages are sufficient to prevent Cd-induced growth restriction, ID, IDA, and MASLD in offspring at postnatal day 21 (PND21). Our findings suggest that Fe supplementation may be a viable therapy to prevent these developmental effects of maternal Cd exposure.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hill-Type Equation Reveals the Regulatory Principle of Target Protein Expression Led by p53 Pulsing","authors":"Xiaomin Shi","doi":"10.1096/fba.2024-00220","DOIUrl":"https://doi.org/10.1096/fba.2024-00220","url":null,"abstract":"<p>The central dogma indicates the basic direction of gene expression pathways. For activated gene expression, the quantitative relationship between various links from the binding of transcription factors (TFs) to DNA to protein synthesis remains unclear and debated. There is consensus that at a steady state, protein levels are largely determined by the mRNA level. How can we find this steady state? Taking p53 as an example, based on the previously discovered Hill-type equation that characterizes mRNA expression under p53 pulsing, I proved that the same equation can be used to describe the average steady state of target protein expression. Therefore, at steady state, the average fold changes in mRNA and protein expression under TFs pulsing were the same. This consensus has been successfully demonstrated. For the p53 target gene <i>BAX</i>, the observed fold changes in mRNA and protein expression were 1.40 and 1.28, respectively; the fold changes in mRNA and protein expression calculated using the Hill-type equation were both 1.35. Therefore, using this equation, we can not only fine-tune gene expression, but also predict the proteome from the transcriptome. Furthermore, by introducing two quantitative indicators, we can determine the degree of accumulation and stability of protein expression.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmalogen as a Bioactive Lipid Drug: From Preclinical Research Challenges to Opportunities in Nanomedicine","authors":"Yu Wu,&nbsp;Yuru Deng,&nbsp;Borislav Angelov,&nbsp;Angelina Angelova","doi":"10.1096/fba.2025-00010","DOIUrl":"https://doi.org/10.1096/fba.2025-00010","url":null,"abstract":"<p>Plasmalogens are natural glycerophospholipids that account for approximately 15%–20% (mol%) of human tissues' cellular membrane phospholipid composition. They play an important role in lipid membrane organization and function, including acting as endogenous antioxidants. Plasmalogens contain a vinyl-ether linked alkyl chain at position sn-1, characteristic of vinyl-ether lipids, and often a polyunsaturated fatty acid (PUFA) acyl chain at position sn-2 of the glycerol backbone. The role of plasmalogens in various patho-physiological processes has been revealed in recent years, including various neurological disorders associated with plasmalogen deficiency. Plasmalogen Replacement Therapy (PRT) is a therapeutic approach that aims to increase plasmalogen levels in the body and address plasmalogen deficiencies in diseases such as age-related neurodegenerative diseases, cardiovascular diseases, certain genetic peroxisomal disorders, and metabolic disorders. We provide a detailed overview of current information on the role of plasmalogens in health and disease. We summarize various strategies for regulating plasmalogen levels and highlight recent advancements in therapeutic applications. We also focus on the potential application of nanomedicine for treating disorders associated with PUFA-lipid and plasmalogen deficiencies.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of NRP1/HDAC4/CREB/RIPK1 Axis in SARS-CoV2 S1 Spike Subunit-Induced Neuronal Toxicity","authors":"Luca Sanguigno,&nbsp;Natascia Guida,&nbsp;Mariarosaria Cammarota,&nbsp;Silvia Ruggiero,&nbsp;Angelo Serani,&nbsp;Francesca Galasso,&nbsp;Vincenzo Pizzorusso,&nbsp;Francesca Boscia,&nbsp;Luigi Formisano","doi":"10.1096/fba.2025-00005","DOIUrl":"https://doi.org/10.1096/fba.2025-00005","url":null,"abstract":"<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is associated with neurological symptoms, but the molecular mechanisms have not yet been identified. Since the S1 subunit (S1) of the envelope of the SARS-CoV2 Spike glycoprotein can reach the CNS, we studied whether S1 could cause neuronal death in a direct manner. Transfection of the S1 plasmid in SH-SY5Y cells reduces cell survival in a time-dependent manner, whereas the overexpression of the S2 subunit does not. Notably, isoform 4 of histone deacetylases (HDAC4) is involved in S1-induced cell toxicity, whereas, among the different cell death drug inhibitors, only the necroptosis blocker Necrostatin-1 counteracted the neurodetrimental effect of S1. Coherently, an increase of the necroptosis marker receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and a reduction of its transcriptional repressor cAMP response element-binding protein (CREB) occur in S1-overexpressing cells. Noteworthy, HDAC4 interacts with CREB determining its protein reduction and the consequent increase of RIPK1. Importantly, we found that S1 recombinant protein (S1rp), through the internalization of the surface receptor Neuropilin 1 (NRP1), but not via Angiotensin-Converting Enzyme 2 (ACE 2) receptor, enters the cytoplasm causing cell death in differentiated SH-SY5Y cells. Finally, in accordance with other papers demonstrating that COVID-19 patients had more severe ischemic strokes with worse outcomes, we found that S1rp increased oxygen glucose deprivation/reoxygenation-induced toxicity in an additive manner, via the NRP1/HDAC4/CREB/RIPK1 pathway. In conclusion, this is the first report identifying the molecular determinants involved in Spike S1-induced neurotoxicity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle","authors":"Alexander Ahn,&nbsp;Jeongjin J. Kim,&nbsp;Aaron L. Slusher,&nbsp;Jeffrey Y. Ying,&nbsp;Eric Y. Zhang,&nbsp;Andrew T. Ludlow","doi":"10.1096/fba.2025-00007","DOIUrl":"https://doi.org/10.1096/fba.2025-00007","url":null,"abstract":"<p>Alternative splicing (AS) is a highly conserved posttranscriptional mechanism, generating mRNA variants to diversify the proteome. Acute endurance exercise appears to transiently perturb AS in skeletal muscle, but transcriptome-wide responses are not well defined. We aimed to better understand differential AS (DAS) and differential isoform expression (DIE) in skeletal muscle by comparing short-read (SRS) and long-read RNA sequencing (LRS) data. Publicly accessible SRS of clinical exercise studies were extracted from the Gene Expression Omnibus. Oxford Nanopore LRS was performed on mouse gastrocnemius before and following treadmill exercise (30 m running, <i>n</i> = 5 mice/group, 20 total, 10 weeks old). Differential gene expression (DGE) and DIE were analyzed and validated using RT-PCR and immunoblots. Both SRS and LRS illustrated significant DGE in skeletal muscle postexercise, including 89 RNA-binding proteins (RBPs). rMATS analysis of SRS revealed that exon-skipping and intron-retaining events were the most common. Swan analysis of LRS revealed several common genes across postexercise cohorts with significant DAS but no DGE: 13 exercise-associated genes, including <i>mSirt2</i> (24.5% shift at 24 h postexercise [24pe], <i>p</i> = 0.005); 61 RBPs, including <i>mHnrnpa3</i> (28.5% at 24pe, <i>p</i> = 0.02), <i>mHnrnpa1</i> (30.6% at 24pe, <i>p</i> = 0.004), and <i>mTia1</i> (53.6% at 24pe, <i>p</i> = 0.004). We illustrated that acute endurance exercise can elicit changes in AS-related responses and RBP expression in skeletal muscle, especially at 24pe. SRS is a powerful tool for analyzing DGE but lacks isoform detection, posing a major gap in knowledge of “hidden” genes with no transcriptional but significant DIE and protein expression changes. Additionally, LRS can uncover previously unknown transcript diversity and mechanisms influencing endurance exercise adaptations and responses.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 8","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMMD10 Regulates Angiogenesis and Bone Formation via Rap1 Signaling Pathway","authors":"Peiran Li,&nbsp;Yanxi Li","doi":"10.1096/fba.2024-00159","DOIUrl":"https://doi.org/10.1096/fba.2024-00159","url":null,"abstract":"<p>Copper metabolism MURR1 domain protein 10 (COMMD10) regulates numerous biological processes that are essential for cellular homeostasis. However, the role of COMMD10 in angiogenesis and bone formation remains unexplored. We constructed a COMMD10 knockdown model in endothelial cells and determined the influence of COMMD10 on angiogenesis and bone formation. Our results indicate that COMMD10 knockdown enhances vascular formation by influencing the expression of genes and proteins related to angiogenesis in endothelial cells. In addition, endothelial cells expressing low levels of COMMD10 facilitate bone formation by secreting pro-osteogenic factors. Further, the Rap1 signaling pathway is activated under low COMMD10 conditions. Double knockdown of RAP1B and COMMD10 attenuated the angiogenic ability of endothelial cells. In summary, our research demonstrates that low COMMD10 expression promotes angiogenesis and bone formation through the Rap1 signaling pathway.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}