Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Mechanism of mitochondrial [2Fe-2S] cluster biosynthesis","authors":"Kristian Want,&nbsp;Benoit D'Autréaux","doi":"10.1016/j.bbamcr.2024.119811","DOIUrl":"10.1016/j.bbamcr.2024.119811","url":null,"abstract":"<div><p>Iron‑sulfur (Fe-S) clusters constitute ancient cofactors that accompany a versatile range of fundamental biological reactions across eukaryotes and prokaryotes. Several cellular pathways exist to coordinate iron acquisition and sulfur mobilization towards a scaffold protein during the tightly regulated synthesis of Fe-S clusters. The mechanism of mitochondrial eukaryotic [2Fe-2S] cluster synthesis is coordinated by the Iron-Sulfur Cluster (ISC) machinery and its aberrations herein have strong implications to the field of disease and medicine which is therefore of particular interest. Here, we describe our current knowledge on the step-by-step mechanism leading to the production of mitochondrial [2Fe-2S] clusters while highlighting the recent developments in the field alongside the challenges that are yet to be overcome.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 8","pages":"Article 119811"},"PeriodicalIF":4.6,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERK5 mediates pro-tumorigenic phenotype in non-small lung cancer cells induced by PGE2","authors":"Arianna Filippelli ,&nbsp;Valerio Ciccone ,&nbsp;Cinzia Del Gaudio ,&nbsp;Vittoria Simonis ,&nbsp;Maria Frosini ,&nbsp;Ignazia Tusa ,&nbsp;Alessio Menconi ,&nbsp;Elisabetta Rovida ,&nbsp;Sandra Donnini","doi":"10.1016/j.bbamcr.2024.119810","DOIUrl":"10.1016/j.bbamcr.2024.119810","url":null,"abstract":"<div><p>Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting approximately 84 % of all lung cancer cases. The role of inflammation in the initiation and progression of NSCLC tumors has been the focus of extensive research. Among the various inflammatory mediators, prostaglandin E2 (PGE2) plays a pivotal role in promoting the aggressiveness of epithelial tumors through multiple mechanisms, including the stimulation of growth, evasion of apoptosis, invasion, and induction of angiogenesis. The Extracellular signal-Regulated Kinase 5 (ERK5), the last discovered member among conventional mitogen-activated protein kinases (MAPK), is implicated in cancer-associated inflammation. In this study, we explored whether ERK5 is involved in the process of tumorigenesis induced by PGE2. Using A549 and PC9 NSCLC cell lines, we found that PGE2 triggers the activation of ERK5 via the EP1 receptor. Moreover, both genetic and pharmacological inhibition of ERK5 reduced PGE2-induced proliferation, migration, invasion and stemness of A549 and PC9 cells, indicating that ERK5 plays a critical role in PGE2-induced tumorigenesis. In summary, our study underscores the pivotal role of the PGE2/EP1/ERK5 axis in driving the malignancy of NSCLC cells in vitro. Targeting this axis holds promise as a potential avenue for developing novel therapeutic strategies aimed at controlling the advancement of NSCLC.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119810"},"PeriodicalIF":4.6,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E3 ubiquitin ligases SMURF1 and HECW1 regulate hepcidin-induced degradation of ferroportin in HeLa cells","authors":"Camille J. Link ,&nbsp;Oriana Marques ,&nbsp;Julia D. Knopf ,&nbsp;Marius K. Lemberg ,&nbsp;Martina U. Muckenthaler","doi":"10.1016/j.bbamcr.2024.119803","DOIUrl":"10.1016/j.bbamcr.2024.119803","url":null,"abstract":"","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119803"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[4Fe-4S]-dependent enzymes in non-redox tRNA thiolation","authors":"Sylvain Gervason ,&nbsp;Sambuddha Sen ,&nbsp;Marc Fontecave,&nbsp;Béatrice Golinelli-Pimpaneau","doi":"10.1016/j.bbamcr.2024.119807","DOIUrl":"10.1016/j.bbamcr.2024.119807","url":null,"abstract":"<div><p>Post-transcriptional modification of nucleosides in transfer RNAs (tRNAs) is an important process for accurate and efficient translation of the genetic information during protein synthesis in all domains of life. In particular, specific enzymes catalyze the biosynthesis of sulfur-containing nucleosides, such as the derivatives of 2-thiouridine (s²U), 4-thiouridine (s⁴U), 2-thiocytidine (s²C), and 2-methylthioadenosine (ms²A), within tRNAs. Whereas the mechanism that has prevailed for decades involved persulfide chemistry, more and more tRNA thiolation enzymes have now been shown to contain a [4Fe-4S] cluster. This review summarizes the information over the last ten years concerning the biochemical, spectroscopic and structural characterization of [4Fe-4S]-dependent non-redox tRNA thiolation enzymes.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119807"},"PeriodicalIF":4.6,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001502/pdfft?md5=f03fb5101a413a8d9be7bbaf2a3d53bc&pid=1-s2.0-S0167488924001502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial mitochondrial transplantation (AMT) reverses aging of mesenchymal stromal cells and improves their immunomodulatory properties in LPS-induced synoviocytes inflammation","authors":"Lynda Bourebaba ,&nbsp;Nabila Bourebaba ,&nbsp;Larry Galuppo ,&nbsp;Krzysztof Marycz","doi":"10.1016/j.bbamcr.2024.119806","DOIUrl":"10.1016/j.bbamcr.2024.119806","url":null,"abstract":"<div><p>Nowadays, regenerative medicine techniques are usually based on the application of mesenchymal stromal cells (MSCs) for the repair or restoration of injured damaged tissues. However, the effectiveness of autologous therapy is limited as therapeutic potential of MSCs declines due to patient's age, health condition and prolonged <em>in vitro</em> cultivation as a result of decreased growth rate. For that reason, there is an urgent need to develop strategies enabling the <em>in vitro</em> rejuvenation of MSCs prior transplantation in order to enhance their <em>in vivo</em> therapeutic efficiency.</p><p>In presented study, we attempted to mimic the naturally occurring mitochondrial transfer (MT) between neighbouring cells and verify whether artificial MT (AMT) could reverse MSCs aging and improve their biological properties. For that reason, mitochondria were isolated from healthy donor equine adipose-derived stromal cells (ASCs) and transferred into metabolically impaired recipient ASCs derived from equine metabolic syndrome (EMS) affected horses, which were subsequently subjected to various analytical methods in order to verify the cellular and molecular outcomes of the applied AMT.</p><p>Mitochondria recipient cells were characterized by decreased apoptosis, senescence and endoplasmic reticulum stress while insulin sensitivity was enhanced. Furthermore, we observed increased mitochondrial fragmentation and associated PARKIN protein accumulation, which indicates on the elimination of dysfunctional organelles <em>via</em> mitophagy. AMT further promoted physioxia and regulated autophagy fluxes. Additionally, rejuvenated ASCs displayed an improved anti-inflammatory activity toward LPS-stimulated synoviocytes. The presented findings highlight AMT as a promising alternative and effective method for MSCs rejuvenation, for potential application in autologous therapies in which MSCs properties are being strongly deteriorated due to patients' condition.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119806"},"PeriodicalIF":4.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001496/pdfft?md5=88436e63d012b0eafc19187a2e4cc462&pid=1-s2.0-S0167488924001496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SOCS2 alleviates myocardial fibrosis by reducing nuclear translocation of β-catenin","authors":"Ming Yuan ,&nbsp;Hongjie Shi ,&nbsp;Bin Wang ,&nbsp;Jie Cai ,&nbsp;Wenjun Yu ,&nbsp;Wei Wang ,&nbsp;Qiaofeng Qian ,&nbsp;Yumou Wang ,&nbsp;Xianwu Zhou ,&nbsp;Jinping Liu","doi":"10.1016/j.bbamcr.2024.119804","DOIUrl":"10.1016/j.bbamcr.2024.119804","url":null,"abstract":"<div><h3>Background</h3><p>Myocardial fibrosis is an important pathological feature of dilated cardiomyopathy (DCM). The roles of SOCS2 in fibrosis of different organs are controversial. Herein, we investigated the function and potential mechanism of SOCS2 in myocardial fibrosis.</p></div><div><h3>Methods</h3><p>Bioinformatics, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), real-time fluorescence quantitative PCR (qPCR), rat primary myocardial fibroblasts (rCFs) culture, doxorubicin (DOX) induced mouse dilated cardiomyopathy (DCM) model, and in vivo adeno-associated virus (AAV) infection were used to explore the role of SOCS2 in DCM.</p></div><div><h3>Results</h3><p>Bioinformatics analysis showed that SOCS2 was positively correlated with fibrosis related factors. SOCS2 was significantly upregulated in patients and mice with DCM. In vivo experiments showed that targeted inhibition of cardiac SOCS2 could improve mouse cardiac function and alleviate myocardial fibrosis. Further research demonstrated that SOCS2 promoted the transformation of myofibroblasts. Knockdown of SOCS2 reduced the nuclear localization of β-catenin, which inhibited the fibrogenic effect of Wnt/β-catenin pathway. In addition, bioinformatics analysis suggested that lymphoid enhancer binding factor 1 (LEF1) was significantly positively correlated with SOCS2. Finally, dual luciferase assays demonstrated that LEF1 could bind to the promoter region of SOCS2, thereby mediating its transcriptional activation.</p></div><div><h3>Conclusion</h3><p>SOCS2 could activate the Wnt/β-catenin by regulating the nuclear translocation of β-catenin, which induces the transcriptional activation of SOCS2. Overall, these results indicated a positive feedback activation phenomenon between SOCS2, β-catenin and LEF1 in DCM. These results suggested that inhibition of SOCS2 could effectively alleviate the progression of myocardial fibrosis and improve cardiac function.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119804"},"PeriodicalIF":4.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSlc17a5 controlled by VLDLR/QKI pathway regulated the choroidal angiogenesis","authors":"Fang Deng,&nbsp;Chong-Bo Chen,&nbsp;Huiping Li,&nbsp;Shaofen Huang,&nbsp;Ciyan Xu,&nbsp;Xiaoqiang Xiao","doi":"10.1016/j.bbamcr.2024.119802","DOIUrl":"10.1016/j.bbamcr.2024.119802","url":null,"abstract":"<div><h3>Rationale</h3><p>Very-low-density lipoprotein receptor (VLDLR) involves in ocular neovascularization, a major cause of severe vision loss. However, the underlying molecular mechanisms were not completely clarified. Here, we aimed to investigate roles of circular RNAs (circRNAs) in VLDLR-associated ocular neovascularization.</p></div><div><h3>Methods</h3><p><em>Vldlr</em> knockout (<em>Vldlr</em>-/-, ko), <em>Robo4</em> knockout (<em>Robo4</em>-/-, ko) and wild-type (WT) mice were used. Mouse model of oxygen induced retinopathy (OIR) and high-throughput sequence were performed to profile the differential expression of circRNA and transcripts. RNase R treatment, Sanger PCR sequencing and quantitative polymerase chain reaction (qPCR) were used to validate candidate circRNAs and their expression patterns. Choroidal sprouting assay ex vivo and laser induction choroid neovascularization were used to determine the expression and functions of QKI/CircSlc17a5 on choroidal neovascularization.</p></div><div><h3>Results</h3><p>In macrophage and ocular tissues derived from <em>Vldlr</em> (<em>Vldlr-/-,Vldlr ko</em>) or <em>Robo4</em> (<em>Robo4-/-,Robo4 ko</em>) deficiency as well as wild-type (WT) mice, Quaking (<em>Qki)</em> expression was significantly down-regulated in <em>Vldlr</em> deficiency compared to WT and <em>Robo4</em> deficiency groups. Ectopic VLDLR expression or Reelin stimulation increased expression of QKI in bEnd.3 cells. Circular RNA sequencing uncovered that VLDLR regulated the biogenesis of certain circular RNAs, including the circSlc17a5. The number of Circular RNAs increased in mice treated with OIR. QKI mediated the biogenesis of circSlc17a5, which was an important regulator of choroidal angiogenesis.</p></div><div><h3>Conclusion</h3><p>CircSlc17a5 regulated by VLDLR/QKI plays important roles in the choroidal angiogenesis.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119802"},"PeriodicalIF":4.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001459/pdfft?md5=20b99ccf404544a7cfb7423752401259&pid=1-s2.0-S0167488924001459-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin enhances iron bioavailability in HepG2 cells by downregulating hepcidin through mTOR, C/EBPα and HIF-1α","authors":"Romina Eugenia Maltaneri,&nbsp;María Eugenia Chamorro,&nbsp;Silvana Estela Gionco,&nbsp;Alcira Beatriz Nesse,&nbsp;Daniela Cecilia Vittori","doi":"10.1016/j.bbamcr.2024.119800","DOIUrl":"10.1016/j.bbamcr.2024.119800","url":null,"abstract":"<div><p>The regulation of iron (Fe) levels is essential to maintain an adequate supply for erythropoiesis, among other processes, and to avoid possible toxicity. The liver-produced peptide hepcidin is regarded as the main regulator of Fe absorption in enterocytes and release from hepatocytes and macrophages, as it impairs Fe export through ferroportin. The glycoprotein erythropoietin (Epo) drives erythroid progenitor survival and differentiation in the bone marrow, and has been linked to the mobilization of Fe reserves necessary for hemoglobin production. Herein we show that Epo inhibits hepcidin expression directly in the HepG2 hepatic cell line, thus leading to a decrease in intracellular Fe levels. Such inhibition was dependent on the Epo receptor-associated kinase JAK2, as well as on the PI3K/AKT/mTOR pathway, which regulates nutrient homeostasis. Epo was also found to decrease binding of the C/EBP-α transcription factor to the hepcidin promoter, which could be attributed to an increased expression of its inhibitor CHOP. Epo did not only hinder the stimulating effect of C/EBP-α on hepcidin transcription, but also favored hepcidin inhibition by HIF-1α, by increasing is nuclear translocation as well as its protein levels. Moreover, in assays with the inhibitor genistein, this transcription factor was found necessary for Epo-induced hepcidin suppression. Our findings support the involvement of the PI3K/AKT/mTOR pathway in the regulation of Fe levels by Epo, and highlight the contrasting roles of the C/EBP-α and HIF-1α transcription factors as downstream effectors of the cytokine in this process.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119800"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression","authors":"Yasuo Okamoto ,&nbsp;Keisuke Kitakaze ,&nbsp;Yasuhiro Takenouchi ,&nbsp;Rena Matsui ,&nbsp;Daisuke Koga ,&nbsp;Ryo Miyashima ,&nbsp;Hironobu Ishimaru ,&nbsp;Kazuhito Tsuboi","doi":"10.1016/j.bbamcr.2024.119798","DOIUrl":"10.1016/j.bbamcr.2024.119798","url":null,"abstract":"<div><p>Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused by myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets of current antifibrotic drugs, no drug has yet been approved to stop fibrosis progression. Herein, we aimed to identify GPCRs with profibrotic effects. In gene expression analysis of mouse lungs with induced fibrosis, eight GPCRs were identified, showing a &gt;2-fold increase in mRNA expression after fibrosis induction. Among them, we focused on Gpr176 owing to its significant correlation with a myofibroblast marker α-smooth muscle actin (αSMA), the profibrotic factor transforming growth factor β1 (TGFβ1), and collagen in a human lung gene expression database. Similar to the lung fibrosis model, increased <em>Gpr176</em> expression was also observed in other organs affected by fibrosis, including the kidney, liver, and heart, suggesting its role in fibrosis across various organs. Furthermore, fibroblasts abundantly expressed Gpr176 compared to alveolar epithelial cells, endothelial cells, and macrophages in the fibrotic lung. GPR176 expression was unaffected by TGFβ1 stimulation in rat renal fibroblast NRK-49 cells, whereas knockdown of Gpr176 by siRNA reduced TGFβ1-induced expression of αSMA, fibronectin, and collagen as well as Smad2 phosphorylation. This suggested that Gpr176 regulates fibroblast activation. Consequently, Gpr176 acts in a profibrotic manner, and inhibiting its activity could potentially prevent myofibroblast differentiation and improve fibrosis. Developing a GPR176 inverse agonist or allosteric modulator is a promising therapeutic approach for fibrosis.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119798"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001411/pdfft?md5=5af8dcb025784d23175bb8f54ffefe0e&pid=1-s2.0-S0167488924001411-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-angiogenic and anti-vasculogenic mimicry effects of GN25 in endothelial and glioma cells","authors":"Zhi-Hong Wen ,&nbsp;Long Chang ,&nbsp;San-Nan Yang ,&nbsp;Chen-Ling Yu ,&nbsp;Fang-Yu Tung ,&nbsp;Hsiao-Mei Kuo ,&nbsp;I-Chen Lu ,&nbsp;Chang-Yi Wu ,&nbsp;Po-Chang Shih ,&nbsp;Wu-Fu Chen ,&nbsp;Nan-Fu Chen","doi":"10.1016/j.bbamcr.2024.119799","DOIUrl":"10.1016/j.bbamcr.2024.119799","url":null,"abstract":"<div><h3>Background and purpose</h3><p>Scientists have been exploring anti-angiogenic strategies to inhibit angiogenesis and prevent tumor growth. Vasculogenic mimicry (VM) in glioblastoma multiforme (GBM) poses a challenge, complicating anti-angiogenesis therapy. A novel drug, GN25 (3-[{1,4-dihydro-5,8-dimethoxy-1,4-dioxo-2-naphthalenyl}thio]-propanoic acid), can inhibit tumor formation. This study aims to investigate the microenvironmental effects and molecular mechanisms of GN25 in anti-angiogenesis and anti-VM.</p></div><div><h3>Experimental approach</h3><p>MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the cell viability of different concentrations of GN25 in human umbilical vein endothelial cells (HUVEC) and Uppsala 87 malignant glioma (U87MG) cells. Functional assays were used to investigate the effects of GN25 on angiogenesis-related processes, whereas gelatin zymography, enzyme-linked immunosorbent assays, and Western blotting were utilized to assess the influence on matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) secretion and related signaling pathways.</p></div><div><h3>Key results</h3><p>GN25 suppressed migration, wound healing, and tube formation in HUVECs and disrupted angiogenesis in a rat aorta ring and zebrafish embryo model. GN25 dose-dependently reduced phosphatidylinositol 3-kinase/AKT and inhibited MMP-2/VEGF secretion in HUVECs. In U87MG cells, GN25 inhibited migration, wound healing, and VM, accompanied by a decrease in MMP-2 and VEGF secretion. The results indicate that GN25 effectively inhibits angiogenesis and VM formation in HUVECs and U87MG cells without affecting preexisting vascular structures.</p></div><div><h3>Conclusion and implications</h3><p>This study elaborated GN25's potential as an anti-angiogenic agent by elucidating its inhibitory effects on classical angiogenesis. VM provides valuable insights for developing novel therapeutic strategies against tumor progression and angiogenesis-related diseases. These results indicate the potential of GN25 as a promising candidate for angiogenesis-related diseases.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119799"},"PeriodicalIF":4.6,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}