BMC Molecular and Cell Biology最新文献

{"title":"Effects of irisin on inflammatory and apoptotic markers in the Caco-2 colon cancer cell line.","authors":"Elif Zeynep Ozturk, Ebubekir Bakan, Nurcan Kilic Baygutalp, Zafer Bayraktutan","doi":"10.1186/s12860-026-00568-w","DOIUrl":"10.1186/s12860-026-00568-w","url":null,"abstract":"<p><p>OBJECTIVE: Irisin is a myokine that is secreted by muscle tissue and is recognized for its regulatory effects on inflammation. The objective of this study was to examine the potential anti-inflammatory function of irisin in the context of colon cancer, with a focus on its effects on the Caco-2 cell line. Method: Specifically, pro-inflammatory cytokine levels (IL-6 and TNF-α), apoptotic marker Caspase-3 activity, and changes in the NF-κB signaling pathway were assessed using ELISA assays. RESULTS: The findings of this study indicated a substantial augmentation in IL-6 levels in the 100 nM irisin-treated group in comparison to the control group (p < 0.05). Furthermore, a significant divergence in Caspase-3 activity was observed between the 10 nM and 100 nM irisin groups (p < 0.05). While direct antiproliferative effects of irisin on Caco-2 cells were not evident in analyses of cellular toxicity, a significant increase in Caspase-3 activity suggested activation of apoptotic pathways. Furthermore, the upregulation of NF-κB signaling, which is generally linked to cancer progression through the suppression of apoptosis, was observed following irisin treatment. CONCLUSION: Irisin did not exert a consistent antiproliferative effect in Caco-2 cells under the tested conditions. Instead, irisin exposure was associated with alterations in inflammatory and apoptotic markers, including increased IL-6 and NF-κB levels and modulation of caspase-3 activity. These findings suggest that irisin may act as a context-dependent regulator of inflammatory and apoptotic signaling rather than a direct anti-inflammatory or antiproliferative agent in colon cancer cells. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017402","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":"Dysregulation of caspase-8 and caspase-9 in T-lymphocyte apoptosis: implications for pathogenesis, diagnosis, and therapeutic targeting in psoriatic arthritis.","authors":"Hadeel A Al-Rawaf, Sami A Gabr, Amir Iqbal, Ahmad H Alghadir","doi":"10.1186/s12860-026-00565-z","DOIUrl":"10.1186/s12860-026-00565-z","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND: Apoptotic changes in keratinocytes and alterations in T-lymphocytes were shown to have a role in the progression of psoriatic arthritis (PsA). OBJECTIVES: To determine the possible role of the apoptotic changes in peripheral T-lymphocytes in association with the activity of both caspase-8 and caspase-9, and the expression of B-cell lymphoma 2 (Bcl-2) and Annexin V in the pathogenesis of PsA. In addition, the relationships between these apoptotic-related markers, the clinical severity of PsA, and the expression of inflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-17 (IL-17) were explored. Moreover, the possibility of using these biological parameters as diagnostic biomarkers was considered, especially for therapeutic programs aiming to address both dermatological and rheumatological signs of PsA. METHODS: A total of 105 subjects aged 31–64 years old were invited to participate in this case–control study. Sixty-five subjects were diagnosed with PsA according to the psoriasis area severity index (PASI) score and classification standards like CASPAR (classification criteria for PsA), and twenty healthy subjects were included as a control group. The healthy volunteers underwent a standard annual physical and biochemical analysis for medical insurance and had neither a history of joint disease nor a family history of psoriasis. The patients were classified based on their PASI score into three distinct groups: mild (n = 10; PASI score up to 25), moderate (n = 25; PASI score of ≥ 25), and severe (n = 30; PASI score of ≥ 50). All disease activity parameters, which included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), and rheumatoid factor (RF-IgG), TNF-α and IL-17, health quality, and pain scores, were assessed using colorimetric immunoassays, pre-validated health assessments, and pain score questionnaires. The serum apoptotic enzymes, caspase-8 and caspase-9, Bcl-2, Annexin V and T-lymphocyte apoptosis were assessed using colorimetric immunoassays and culture assays. RESULTS: In this study, about 23.5% of the study subjects with no history of joint or psoriasis disease (n = 20), and 76.5% of the study subjects (n = 65) with a disease duration range of 11.5 ± 7, showed evidence of abnormal skin disorders, with higher scores for PASI and arthritic parameters, including the ESR, Rf-IGg, hs-CRP, and DAS28-ESR scores. Moreover, among the PsA patients, a total of 50% had polyarthritis, 46% had oligoarthritis, and only four had monoarthritis. A total of 50% of the patients had both large and small joint involvement, 40% had small joint involvement, and 10% had large joint involvement. A total of 64% of the patients had an asymmetric pattern of joint involvement, and 36% had a symmetric pattern of joint involvement. The results showed that caspase-8 significantly decreased and both caspase-9 and T-lymphocyte apoptosis (AI) significantly increased in patients with moderate and severe ","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"6"},"PeriodicalIF":3.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12896360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997262","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":"Intracellular Ca²⁺ is not essential for SHH signaling but is promoted by Shh ligand in embryonic fibroblasts.","authors":"Xuanming Shi, Zhaomin Wang, Shupeng Li, Yiming Pan, Bing Shen, Shuzhen Liu","doi":"10.1186/s12860-026-00567-x","DOIUrl":"10.1186/s12860-026-00567-x","url":null,"abstract":"<p><p>BACKGROUND: Sonic Hedgehog (SHH) signaling pathway controls cell proliferation, differentiation, and organ formation. The changes in Ca2+ and their regulatory role in the context of activated SHH signaling have not been fully examined. RESULTS: In this study, we induced activation of the SHH signaling pathway using activators, including Full-length Shh protein (Shh) and N-terminal Shh (ShhN) ligands or a Smoothened agonist (SAG), while concurrently manipulating calcium level by either increasing extracellular Ca2+ concentration or employing BAPTA to chelate intracellular Ca2+. We found that the activation of SHH target genes by the three activators was not affected by low intracellular Ca2+ but inhibited by excess Ca2+. Although both Shh and SAG activate Ca2+ influx via the store-operated calcium entry (SOCE), their effects differ in the presence of BAPTA: Shh directly increases intracellular Ca2+ concentration, whereas the effect of SAG is enhanced by high extracellular Ca2+. CONCLUSIONS: Excessive extracellular Ca2+ impairs SHH signal transduction, whereas intracellular Ca2+ levels have a negligible effect. At normal physiological extracellular Ca2+ concentrations, the depletion of intracellular Ca2+ does not affect SHH signal transduction. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"7"},"PeriodicalIF":3.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997211","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":"Mitochondrial HMGCS1 mediates cisplatin resistance in cervical cancer through regulation of mitochondrial transcription.","authors":"Wenxuan Yang, Shumin Liu, Dandan Shang, Ping Liu, Hongtang Shi, Hongtao Zhang, Chao Zhou","doi":"10.1186/s12860-026-00566-y","DOIUrl":"10.1186/s12860-026-00566-y","url":null,"abstract":"<p><p>Cisplatin resistance remains a major challenge in the treatment of cervical cancer. Here, we identify 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a rate-limiting enzyme in the mevalonate pathway, as a critical regulator of cisplatin resistance through its localization to mitochondria. HMGCS1 preferentially accumulates in the mitochondria of cisplatin-resistant cervical cancer cells, and targeted expression of HMGCS1 to mitochondria, but not to the nucleus or cytosol, is sufficient to confer cisplatin resistance. Mechanistically, mitochondrial HMGCS1 associates with the D-loop region of mitochondrial DNA (mtDNA) and is required for the stable binding of the core transcription machinery components POLRMT, TFAM, and TFB2M. This regulatory function is important for mitochondrial respiratory capacity through its critical role in the transcription of mtDNA-encoded respiratory complex subunits. Genetic depletion or pharmacological inhibition of HMGCS1 disrupts mitochondrial transcription, impairs respiratory function, and re-sensitizes resistant cells to cisplatin. Moreover, combined treatment with cisplatin and inhibitors targeting either HMGCS1 or mitochondrial transcription exhibits synergistic effects against cisplatin-resistant cervical cancer cells. Our findings reveal an unexpected role for HMGCS1 as a non-canonical regulator of mitochondrial transcription and establish the HMGCS1-mitochondrial transcription axis as a promising therapeutic target to overcome cisplatin resistance in cervical cancer.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"5"},"PeriodicalIF":3.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988090","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":"The nascent RNA labelling compound 5-ethynyl uridine (EU) integrates into DNA in some animals.","authors":"Malin A Kjosavik, Katherine L P Downham, Ruth Styfhals, Leonie Adelmann, Marios Chatzigeorgiou, Florian Raible, Pawel Burkhardt, Fergal O'Farrell, Patrick R H Steinmetz, Kathrin Garschall","doi":"10.1186/s12860-025-00560-w","DOIUrl":"10.1186/s12860-025-00560-w","url":null,"abstract":"<p><p>BACKGROUND: The detection of de novo synthesized mRNA transcripts is crucial for understanding the regulation of eukaryotic transcription. Using nucleoside or nucleotide analogues to label nascent RNA is potentially jeopardized by the ubiquitous presence of ribonucleotide reductase enzymes (RNRs) that can convert ribonucleotides into 2’-deoxyribonucleotides, the building blocks of DNA. Despite this challenge, the uridine analogue 5-ethynyl uridine (EU) has been commercialized and routinely used as specific label for nascent RNAs. Here, we employ confocal imaging, flow cytometry and biochemistry methods to study the specificity of EU to label RNA in six different animal species. RESULTS: We demonstrate that EU integrates as expected predominantly into RNA of human embryonic kidney cell line (HEK293T), the Drosophila wing disc and the comb jelly Mnemiopsis leidyi. In contrast, we found that EU predominantly labels DNA in the sea anemones Nematostella vectensis and Exaiptasia diaphana, and the polychaete Platynereis dumerilii. In Nematostella, we show that inhibiting RNR by hydroxyurea abolishes cell proliferation and the incorporation of EU into DNA. Alternative compounds for labelling nascent RNA, such as 5-ethynyl cytidine (EC), 5-ethynyl uridine triphosphate (EUTP) or 2-ethynyl adenosine (EA) show similarly low specificity for RNA in Nematostella. CONCLUSIONS: Our findings raise concerns about the specificity of ethynylated nucleosides and nucleotides, including EU, to label RNA in some animals. We therefore suggest good practice guidelines help identifying unintentional DNA labelling when using EU to label nascent RNA. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"4"},"PeriodicalIF":3.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843559","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":"Related Dictyostelium G protein subunits Gα1 and Gα2 have different roles in chemotaxis and transcription factor regulation.","authors":"Nicholas M Kiger, Nicholas W Mason, Md Ikram Rafid, Jeffrey A Hadwiger","doi":"10.1186/s12860-025-00562-8","DOIUrl":"10.1186/s12860-025-00562-8","url":null,"abstract":"<p><p>Gα subunits provide important contributions to the specificity of signaling pathways that are regulated by G protein-coupled receptors. The Dictyostelium discoideum Gα2 subunit mediates chemotactic responses to cAMP including the activation of the atypical MAPK, Erk2, and translocation of the transcription factor GtaC but some of these responses partially occur in the absence of the Gα2 subunit suggesting a Gα2 subunit-independent mechanism. The Gα1 subunit is the most closely related paralog of the Gα2 subunit making it a possible candidate for overlapping functions. Heterologous expression of Gα1 in gα2− cells did not rescue cAMP chemotaxis or other gα2− phenotypes suggesting no functional overlap between these subunits. Loss of the Gα1 subunit resulted in a slight delay in multicellular development on nonnutrient agar and a growth increase on bacterial lawns in both the parental and gα2− strains. Both gα1− and gα2− cells grew to stationary phase in axenic medium earlier than their parental strain suggesting both subunits might mediate responses to nutrient limitations. The loss of Gα1 function resulted in a marginal impact on the translocation of GtaC but in gα2− cells the absence of Gα1 enhanced the translocation of GtaC. These results indicate that the Gα1 and Gα2 subunits are not functionally redundant but could possibly interact with other proteins common to both signaling pathways. This study also suggests the presence of another cAMP stimulated pathway that can mediate the translocation of GtaC.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"2"},"PeriodicalIF":3.0,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833006","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":"Molecular architecture of mesoderm cells across early to middle stage of human embryo development at single-cell resolution.","authors":"Wei Zhang, Haiyan Yu, Zhibin Zhang, Dandan Li, Yane Yang, Wei Shi, Wenting Li, Yan Jiang, Wenlong Hu, Zhipeng Zeng, Xinqiong Liu, Zhanye Zheng, Minglin Ou, Donge Tang, Yong Dai","doi":"10.1186/s12860-025-00561-9","DOIUrl":"10.1186/s12860-025-00561-9","url":null,"abstract":"<p><strong>Background: </strong>The differentiation of mesodermal cells (MCs) in the early stage of embryonic development contributes to the organogenesis of several core organs. However, the single-cell molecular architecture of MCs and the key molecular events during the differentiation remain unclear.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (RNA sequencing) and single-cell assay for transposase-accessible chromatin (ATAC-Seq) to analyze the developmental features of MCs to heart, kidney, spleen, liver, and brain in human embryos at gestational ages 7-17 weeks.</p><p><strong>Results: </strong>We found that EGR1 might be relevant to the differentiation of heterogeneous MC sub-clusters. Meanwhile, RPL10P9⁺PTMAP5⁺ MCs had the closest expression profiling with endocardial cells. NDUFA4L2⁺A2M⁺ MCs presented the potentials to form endothelial cells (ECs) and hematopoietic stem cells, and MEF2C might be involved in this process.</p><p><strong>Conclusions: </strong>These findings provide insights into the molecular architecture and lineage progression of MCs during early human embryonic organogenesis, offering a valuable reference for regenerative medicine and organ bioengineering.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"3"},"PeriodicalIF":2.7,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833014","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":"Actomyosin dynamics in detached cells: linking clutch model to cell migration and cytokinesis.","authors":"Shigehiko Yumura, Yumi Kikuta, Go Itoh","doi":"10.1186/s12860-025-00563-7","DOIUrl":"10.1186/s12860-025-00563-7","url":null,"abstract":"<p><p>BACKGROUND: Cortical retrograde flow of actomyosin plays a critical role in cell migration and cytokinesis. While such flows have been extensively studied in adherent cells, their underlying mechanisms in non-adherent conditions remain poorly understood. In this study, we investigated actomyosin dynamics in Dictyostelium cells detached from the substratum, with a focus on cytoskeletal turnover and the applicability of the clutch hypothesis. RESULTS: Detached cells exhibited robust retrograde flows of actin and myosin II filaments within the cell cortex, moving at identical velocities. In contrast, membrane components and particles attached to the cell surface showed no movement, suggesting that the flows are driven by cortical actomyosin rather than membrane trafficking. Inhibition of actin polymerization completely abolished the flows, while myosin II inhibition had only a minor effect, indicating that actin polymerization is the primary driver. Flow velocities gradually decreased from the anterior to the posterior, consistent with a model in which actin filaments are pushed rearward rather than pulled from the back. Flow velocity was inversely proportional to cell migration speed, and nascent adhesion foci also moved retrogradely, supporting the clutch hypothesis, although Dictyostelium cells have neither canonical integrins nor well-defined extracellular matrix. Photobleaching experiments revealed that actin and myosin II filaments undergo turnover and recycling near the posterior. During cytokinesis under non-adherent conditions, cortical flows from the poles to the equator were significantly enhanced, and membrane components remained static. The clutch hypothesis may explain also the cortical flow and contractile ring formation during cytokinesis. CONCLUSIONS: Our findings demonstrate that detachment from the substratum induces dynamic, turnover-dependent actomyosin flows. These flows are primarily driven by actin polymerization and are consistent with the clutch hypothesis, which helps explain both cell migration and contractile ring formation during cytokinesis. This study expands the applicability of the clutch model and highlights the dynamic nature of the cytoskeleton in non-adherent cells. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":" ","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817689","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":"Dictyostelium discoideum chemotaxis is altered by hypoxia to orient streaming toward higher oxygen levels.","authors":"Satomi Hirose, Julie Hesnard, Kenichi Funamoto, Jean-Paul Rieu, Christophe Anjard","doi":"10.1186/s12860-025-00557-5","DOIUrl":"10.1186/s12860-025-00557-5","url":null,"abstract":"<p><p>BACKGROUND: Dictyostelium discoideum (Dd) exhibits a unique life cycle marked by its transition from single-cell amoeboid movement to multicellular development in response to environmental stimuli. While its chemotactic response to cyclic adenosine monophosphate (cAMP) has been extensively studied, experiments are usually carried out in a high oxygen (O2) environment (21% O2, also called normoxia) that might not reflect the natural condition for a soil amoeba as low O2 (hypoxia) is common underground. Our recent research has unveiled a novel phenomenon termed aerotaxis, wherein Dd cells migrate towards O2-rich environments under hypoxia. RESULTS: We tested Dd response when submitted to two different stress sources: starvation and hypoxia. While both stresses induced a motile response, namely chemotaxis and aerotaxis, we were able to decouple both types of responses to explore potential shared mechanisms. Importantly, aerotaxis appeared to be operated independently of known chemotactic pathways, demonstrating unique signaling pathways and cellular responses. Aerotaxis contributed to Dd developmental processes by letting cells escape from acute hypoxia. Even though chemotactic response could occur at < 2% O2, it did not lead to well organized or stable streaming. Furthermore, in an O2 gradient, aggregation centers for chemotactic response appeared preferentially at higher O2 levels. RT-qPCR analysis showed that hypoxia only slightly reduced the expression of genes required for chemotactic response, suggesting that the bias toward high O2 might occur at another level. Reoxygenation of cells that had been starved in hypoxic conditions for 18 h allowed rapid aggregation but required de novo protein synthesis. CONCLUSION: Aerotaxis and chemotaxis mechanisms do not interact directly. However, when cells are exposed to both starvation and hypoxia, both mechanisms can be combined to direct the migration of cells toward places with higher O2 levels. As hypoxia is frequent in the soil where Dd usually grows, formation of aggregation centers at or close to the soil surface, where O2 is abundant, will be advantageous. Low O2 levels do not preclude cells from participating in streaming but seem to reduce or delay their ability to produce stable aggregation centers, resulting in a bias favoring centers that form at higher O2 levels. </p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"34"},"PeriodicalIF":3.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437161","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":"EphrinB2 in dental pulp stem cells promotes endothelial cells forming capillary-like cords in a 3D bioprinted hydrogel construct.","authors":"Wen Wang, Junjun Li, Yingying Zhou, Tianshui Ren, Yang Yang, Mengying Li, Hongyu Tian, Penglai Wang, Changyong Yuan","doi":"10.1186/s12860-025-00558-4","DOIUrl":"10.1186/s12860-025-00558-4","url":null,"abstract":"<p><strong>Objectives: </strong>We fabricated a pre-vascularized bioprinted hydrogel construct via coculture of human umbilical vein endothelial cells (HUVECs) and dental pulp stem cells (DPSCs) to investigate the role of ephrinB2 in 3D capillary-like cord self-assemble.</p><p><strong>Materials and methods: </strong>After bioprinting gelatin methacrylate (GelMA) hydrogels, we performed a morphology observation of the inside capillary-like cords, quantitative analysis of branch points and cord length, and examination of pericyte markers in DPSCs. Next, we assessed the influence of DPSCs: HUVECs ratio and degree of functionalization (DoF) of GelMA on the cord formation. To investigate the role of ephrinB2, we used either EphB4/ephrinB2 inhibitor peptide, or knocked down or upregulated ephrinB2 in DPSCs, and evaluated their effects on these cords' generation. Finally, bioprinted hydrogels were subcutaneously transplanted into mice to assess in vitro vascularization.</p><p><strong>Results: </strong>Abundant capillary-like cords containing lumen were found in bioprinted hydrogels. DPSCs wrapped outside the cords and expressed pericyte markers. A 1:3 DPSCs: HUVECs ratio and a 30% DoF of GelMA led to significant increase in branch points and cord length by over 2-fold and 3-fold, respectively. Adding EphB4/ephrinB2 inhibitor peptide or knockdown of ephrinB2 in DPSCs impaired capillary-like cord generation, whereas overexpression of ephrinB2 in DPSCs promoted cord formation. In in vivo experiments, a significant over 3-fold increase in vessel number was observed in hydrogels when ephrinB2 was upregulated in DPSCs compared with wild-type DPSCs.</p><p><strong>Conclusions: </strong>Overexpression of ephrinB2 in DPSCs promoted in vitro capillary-like cord formation and in vivo vascularization in a 3D bioprinted hydrogel.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"33"},"PeriodicalIF":2.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399914","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}