Life sciences最新文献

{"title":"Aberrant WDR5 promotes the progression of cervical cancer through the YAP1- CTGF pathway","authors":"Xiaofeng Ma ,&nbsp;Zhonglei Xu ,&nbsp;Xinrui Wang ,&nbsp;Shiying Sun ,&nbsp;Junhui Zhang ,&nbsp;Ruxian Tang ,&nbsp;Lin Ling ,&nbsp;Bing Wei ,&nbsp;Liangchang Hu ,&nbsp;Enlin Wang","doi":"10.1016/j.lfs.2025.123712","DOIUrl":"10.1016/j.lfs.2025.123712","url":null,"abstract":"<div><h3>Aims</h3><div>WDR5 plays a pivotal role in promoting cancer progression across various malignancies. However, its involvement in cervical cancer remains poorly understood. This study aims to elucidate the mechanisms by which WDR5 drives cervical cancer progression.</div></div><div><h3>Materials and methods</h3><div>Cervical cancer tissues were analyzed to assess WDR5 regulation. <em>In vitro</em> assays evaluated the effects of WDR5 loss-of-function on cell proliferation, migration, and invasion. Mechanistic studies investigated the interaction between WDR5 and YAP1, and the subsequent modulation of CTGF gene expression <em>via</em> histone 3 lysine 4 trimethylation. Xenograft tumor models were utilized to examine the <em>in vivo</em> role of WDR5 in cervical cancer progression.</div></div><div><h3>Key findings</h3><div>WDR5 is significantly upregulated in cervical cancer tissues and correlates with poor prognosis. Loss of WDR5 function markedly suppresses cervical cancer cell proliferation, migration, and invasion <em>in vitro</em>. WDR5 interacts with YAP1, enhancing CTGF expression through histone methylation. <em>In vivo</em>, the oncogenic function of WDR5 is contingent upon the YAP1-CTGF signaling axis.</div></div><div><h3>Significance</h3><div>This study identifies the WDR5/YAP1/CTGF pathway as a key mechanism in cervical cancer progression, suggesting that targeting this axis may provide a promising therapeutic approach.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123712"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ero1a, the most strongly hypoxia-induced protein in PASMCs, promotes the development of hypoxia- and monocrotaline-induced pulmonary hypertension in rats","authors":"Xiaojun Hao ,&nbsp;Hao Li ,&nbsp;Qingli Zeng ,&nbsp;Zhenshun Cheng ,&nbsp;Hongxia Jiang","doi":"10.1016/j.lfs.2025.123754","DOIUrl":"10.1016/j.lfs.2025.123754","url":null,"abstract":"<div><h3>Aims</h3><div>Pulmonary hypertension (PH) is a progressive and life-threatening condition characterized by elevated pressure in the pulmonary circulation, leading to right heart dysfunction and ultimately heart failure. Pulmonary artery smooth muscle cells (PASMCs) are key players in group 3 PH (due to lung diseases and/or hypoxia) progression, where their aberrant proliferation and migration drive vascular remodeling. Dysregulated proteins in PASMCs are critical in PH development. Our research was designed to investigate the most promising potential therapeutic targets for PH.</div></div><div><h3>Materials and methods</h3><div>Proteomics was used to identify the most significantly upregulated protein in PASMCs under hypoxia. siRNA or plasmid transfection was used to silence or overexpress <em>Ero1a.</em> The proliferation, migration, and apoptosis of PASMCs were assessed respectively. Both hypoxia and monocrotaline-induced pulmonary hypertension model were established in animals. The expression of <em>Ero1a</em> was reduced to explore its role in PH. Bioinformatic analysis were conducted to investigate the signaling pathways involved in the disease progression.</div></div><div><h3>Key findings</h3><div><em>Ero1a</em> was confirmed as the most significantly upregulated protein in PASMCs under hypoxia. Silencing <em>Ero1a</em> reduced PASMC proliferation, migration, and apoptosis resistance under both normoxic and hypoxic conditions, while overexpression of <em>Ero1a</em> had the opposite effect. Exposure of rats to hypoxia, along with intraperitoneal injection of MCT solution, induced PH. However, knockdown of <em>Ero1a</em> alleviated all these pathological features. The HIF1-<em>Ero1a</em>-Apelin/APJ signaling axis was speculated to mediate the functional role of <em>Ero1a</em> in PH.</div></div><div><h3>Significance</h3><div>Our study identifies that targeting <em>Ero1a</em> may represent a promising therapeutic strategy for pulmonary hypertension.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123754"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omarigliptin ameliorates cisplatin-induced renal damage: Cross-talk between glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and TXNIP/NLRP3 inflammasome/gasdermin D axis","authors":"Shuruq E. Alsufyani ,&nbsp;Hany H. Arab ,&nbsp;Azza A.K. El-Sheikh ,&nbsp;El-Shaimaa A. Arafa ,&nbsp;Ahmed Fouad Hussein Hashad ,&nbsp;Reham M. Goda ,&nbsp;Tamer M. Naguib ,&nbsp;Maaly A. Abd Elmaaboud ,&nbsp;Mennatallah A. Elkady ,&nbsp;Ahmed M. Kabel","doi":"10.1016/j.lfs.2025.123758","DOIUrl":"10.1016/j.lfs.2025.123758","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Cisplatin is a platinum compound that is effective in the management of neoplastic conditions including testicular, ovarian, and lung malignancies. However, the possible incidence of kidney damage may significantly affect its therapeutic value. Omarigliptin is a dipeptidyl peptidase-4 inhibitor that is effective in treatment of type 2 diabetes mellitus. Interestingly, omarigliptin exhibited significant antioxidant, anti-inflammatory, and pro-autophagic properties in various body tissues. The focus of this research was to evaluate the possible effects of omarigliptin on the renal insult induced by cisplatin and to determine the pathological mechanisms that may precipitate these effects.</div></div><div><h3>Materials and methods</h3><div>This study employed forty Wistar rats which were randomized into 4 equal groups as follows: control group; cisplatin group (injected intraperitoneally with cisplatin at increasing weekly doses at 0.8, 1.6, 3.2, 4.8 mg/kg starting from the end of the first week of the experiments); and 2 other groups treated with cisplatin as described above concomitantly with omarigliptin at 2.5 mg/kg/day and 5 mg/kg/day respectively orally starting 1 week before cisplatin administration and continuing for 6 days after the last cisplatin injection.</div></div><div><h3>Key findings</h3><div>Omarigliptin dose-dependently combatted the renal damaging effects of cisplatin via regulation of glucagon-like peptide-1 levels which subsequently modulates autophagy, the oxidant/antioxidant balance, pyroptosis, and the inflammatory microenvironment of the renal tissues. These favorable responses were associated with dose-dependent significant improvement of the renal morphological changes elicited by cisplatin.</div></div><div><h3>Significance</h3><div>Omarigliptin may be introduced, for the first time, as a promising agent to mitigate the nephrotoxic effects of cisplatin.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123758"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein phosphatase SCP4 regulates temporomandibular joint cartilage development via glucose metabolism","authors":"Jinjin Ma ,&nbsp;Pinger Wang ,&nbsp;Kaiao Zou ,&nbsp;Zhen Zou ,&nbsp;Linyi Zhou ,&nbsp;Guangjun Liu ,&nbsp;Xinyu Wang ,&nbsp;Xinhua Feng ,&nbsp;Xia Lin ,&nbsp;Jianying Feng ,&nbsp;Hongting Jin","doi":"10.1016/j.lfs.2025.123741","DOIUrl":"10.1016/j.lfs.2025.123741","url":null,"abstract":"<div><h3>Objective</h3><div>Despite the growing evidence supporting the regulatory role of small carboxy-terminal domain (CTD) phosphatase 4 (SCP4) in metabolic pathways, limited knowledge exists concerning its involvement and molecular basis in temporomandibular joint (TMJ) cartilage growth, development, and homeostasis maintenance. Therefore, this study aims to investigate the role of SCP4 in chondrogenesis in condylar cartilage.</div></div><div><h3>Methods</h3><div>We generated chondrocyte-specific SCP4 conditional knockout mice (SCP4^Col2Cre). Whole skeletal staining, ABH/OG or HE staining, and immunohistochemistry were employed to compare chondrocyte differentiation and cartilage development between SCP4^Col2Cre and Cre-negative mice during prenatal and postnatal periods. The impact of SCP4 on subchondral bone in mice was assessed using Micro-CT. Additionally, relevant biological functions were evaluated by KEGG and GO enrichment analysis, which further confirmed immunohistochemical staining, Western Blot, RT-PCR and Seahorse experiment.</div></div><div><h3>Results</h3><div>Our findings demonstrated that the deficiency of SCP4 in chondrocytes resulted in defects in condylar chondrogenesis and impaired matrix production. Accordingly, the SCP4^Col2Cre mice exhibited a significant decrease in bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), with an increase in trabecular separation (Tb.Sp). Furthermore, RNA-seq analysis showed the impact of SCP4 deficiency on glucose metabolism. Subsequently, we confirmed that the deficiency of SCP4 resulted in aberrant regulation of glucose transporter 1 (Glut1) and other glucose metabolism-related gene expression throughout prenatal and postnatal development in vivo and in vitro. We further demonstrated in vitro that the deletion of SCP4 led to increased ATP production and extracellular acidification rate (ECAR) levels, while concurrently reducing oxygen consumption rate (OCR) levels.</div></div><div><h3>Conclusion</h3><div>Our study emphasizes the crucial role of SCP4 in regulating prenatal and postnatal TMJ cartilage development, partly through aberrant upregulation of Glut1-mediated glucose metabolism.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123741"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HL-BscPF: Hybrid learning facilitates brain cell auto-identification in multiple pathologies","authors":"Zizheng Suo ,&nbsp;Bocheng Pan ,&nbsp;Hailong Shi ,&nbsp;Linhui Ma ,&nbsp;Yuxiang Zheng ,&nbsp;Wenjie Xu ,&nbsp;Lina Lin ,&nbsp;Enze Zhang ,&nbsp;Lijuan Wang ,&nbsp;Mingzhu Zhang ,&nbsp;Yinyin Qu ,&nbsp;Hui Zheng ,&nbsp;Xingyu Gao ,&nbsp;Cheng Ni","doi":"10.1016/j.lfs.2025.123751","DOIUrl":"10.1016/j.lfs.2025.123751","url":null,"abstract":"<div><h3>Aims</h3><div>The rapidly growing scale and complexity of single-cell transcriptomic data in brain research make it increasingly difficult for traditional methods to extract meaningful insights efficiently, highlighting the need for artificial intelligence.</div></div><div><h3>Materials and methods</h3><div>We presented the Hybrid Learning-based Brain single-cell Prediction Framework (HL-BscPF), designed to automate cell type classification and reveal disease-related pathways in the brain. HL-BscPF integrates ItClust and TOSICA models, combining autoencoder-based dimensionality reduction with transformer architecture to enhance predictive accuracy. HL-BscPF was evaluated using brain scRNA-seq datasets representing various neuropathological states, and its predictive performance was benchmarked against ground-truth annotations.</div></div><div><h3>Key findings</h3><div>Applied to four brain-specific single-cell datasets, including aging, Alzheimer's disease, postoperative cognitive dysfunction, and stroke, HL-BscPF accurately classified cell types and uncovered key functional alterations in neuronal and glial populations. TOSICA showed higher accuracy in large-scale datasets due to its multi-head self-attention capabilities, whereas ItClust performed optimally in cases with lower cell diversity, demonstrating their complementary strengths. By providing precise cell identification and novel insights into brain-specific pathway dysregulation, HL-BscPF offers a powerful tool for extracting meaningful insights from vast single-cell datasets, enabling a deeper understanding of the complex neuropathologies.</div></div><div><h3>Significance</h3><div>HL-BscPF demonstrates exceptional accuracy and interpretability in cell type annotation and functional analysis, uncovering critical disease-related mechanisms. This framework offers a powerful tool for advancing single-cell research in brain pathologies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123751"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimer's disease","authors":"Zhi Tang ,&nbsp;Ting Sha ,&nbsp;Yuanshang Wang ,&nbsp;Yan Xiao ,&nbsp;Yuanting Ding ,&nbsp;Ruiqing Ni ,&nbsp;Xiaolan Qi","doi":"10.1016/j.lfs.2025.123759","DOIUrl":"10.1016/j.lfs.2025.123759","url":null,"abstract":"<div><h3>Aims</h3><div>Isoliquiritigenin is a natural flavonoid extracted from the root of the medicinal herb liquorice. Isoliquiritigenin has various biological effects, including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic activities, and improved mitochondrial function in earlier studies. Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer's disease (AD). Here, we assessed the neuroprotective effects of isoliquiritigenin on a streptozotocin-injected mouse model.</div></div><div><h3>Materials</h3><div>Molecular docking analysis of isoliquiritigenin with mammalian target of rapamycin (mTOR) and ERK2. The mice (<em>n</em> = 27, male) were intracerebroventricularly injected with streptozotocin, treated with isoliquiritigenin (intraperitoneal, 2 days) and assessed using the Morris water maze. Oxidative stress, tau phosphorylation, mitochondrial dysfunction and synaptic impairment were evaluated in the cortex and hippocampal tissues of the mice by using biochemical assays and immunostaining.</div></div><div><h3>Results</h3><div>Isoliquiritigenin treatment mitigated the spatial memory capacity of streptozotocin-injected mice and alleviated tau phosphorylation at Ser396 and Thr231, the production of reactive oxygen species, the intracellular ATP level, the mitochondrial proteins p-DRP1 (S616), Mfn1 and Mfn2, neuronal loss, and synaptic impairment (PSD95, SNAP25). Isoliquiritigenin treatment reduced the levels of mTOR Ser2448 and ERK2 Thr202/Tyr204 and upregulated the level of GSK-3β Ser9 in the cortex and hippocampus of streptozotocin-injected mice.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings suggest that isoliquiritigenin ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, oxidative stress, mitochondrial dysfunction and synaptic impairment by decreasing mTOR and ERK activity and increasing GSK-3β activity.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123759"},"PeriodicalIF":5.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting interferon regulatory factor 7 alleviates renal fibrosis by inhibiting macrophage-to-myofibroblast transition","authors":"Chunnian Ren ,&nbsp;Tao Mi ,&nbsp;Zhaoxia Zhang ,&nbsp;Liming Jin ,&nbsp;Zhaoying Wang ,&nbsp;Xiangpan Kong ,&nbsp;Junyi Luo ,&nbsp;Quan Wang ,&nbsp;Dawei He","doi":"10.1016/j.lfs.2025.123755","DOIUrl":"10.1016/j.lfs.2025.123755","url":null,"abstract":"<div><div>The development of effective therapeutic strategies for renal fibrosis is a key centerpiece in addressing the progression of Chronic Kidney Disease (CKD) to end-stage renal disease (ESRD). Macrophage-to-myofibroblast transition (MMT) is thought to exacerbate the progression of renal fibrosis. Therefore, targeting MMT may be a promising therapeutic strategy for treating renal fibrosis. This study aimed to identify the key effector molecules and specific mechanisms of MMT in renal fibrosis and to provide new ideas for developing drugs for treating renal fibrosis. Analysis of transcriptomic data from Renal interstitial fibrosis (RIF) patients showed that Interferon regulatory factor 7 (IRF7) plays an important role in MMT. Further, the unilateral ureteral obstruction (UUO) model established in IRF7 knockout mice and the MMT model established in IRF7 deficiency macrophage, respectively, found that IRF7 was able to promote MMT by regulating the transcriptional activation of Cathepsin S (CTSS), increasing the number of myofibroblasts, leading to a persistent production of extracellular matrix (ECM) and ultimately exacerbating renal fibrosis. This process is dependent on the regulation of the TGF-β/Smad3 signaling pathway. In addition, we found that human umbilical cord mesenchymal stem cell-derived exosomes mimetic extracellular nanovesicles treatment of renal fibrosis may similarly depend on IRF7-mediated MMT to function. In conclusions, in renal fibrosis, upregulation of IRF7 expression depends on the regulation of the TGF-β/Smad3 signaling pathway and exacerbates renal fibrosis by regulating MMT through the IRF7-CTSS axis. These mechanisms suggest that targeting IRF7 may be the key to future treatment of renal fibrosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123755"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-derived extracellular vesicles: Exploring the pathogenesis and treatment of neuropsychiatric disorders","authors":"Wenjie Zhu ,&nbsp;Yanling Yuan ,&nbsp;Xuan Guan ,&nbsp;Qinglian Xie ,&nbsp;Xueli Sun ,&nbsp;Zaiquan Dong","doi":"10.1016/j.lfs.2025.123750","DOIUrl":"10.1016/j.lfs.2025.123750","url":null,"abstract":"<div><div>The gut microbiome is connected to the pathogenesis of various neuropsychiatric disorders, including cognitive impairment and depression. The gut microbiota can act on the brain through multiple pathways along the gut–brain axis. However, the specific mechanisms are unclear. Bacterial extracellular vesicles (BEVs), bacteria-derived membrane-bound vesicles that can carry a variety of bioactive substances and cross various barriers in the host, are used by bacteria to communicate and interact with the host. Recent studies have shown that BEVs from the gut microbiota are involved in gut-brain communication and may play a role in the pathogenesis and treatment of neuropsychiatric disorders. This review provides an overview of the biogenesis, structure, and function of BEVs and emphasizes their role in the development and treatment of neuropsychiatric disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123750"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation modification: Dawn of research on cornea-related diseases","authors":"Quanhao Pan ,&nbsp;Xiaoning Ge ,&nbsp;Di Wang ,&nbsp;Yuxi He","doi":"10.1016/j.lfs.2025.123757","DOIUrl":"10.1016/j.lfs.2025.123757","url":null,"abstract":"<div><div>DNA methylation is a significant form of epigenetic modification that plays a crucial role in the occurrence and progression of diseases by regulating gene expression. Recent advancements in our understanding of DNA methylation have demonstrated its involvement in corneal damage repair and various corneal diseases. This article reviews the mechanisms and effects of DNA methylation modifications in corneal injury repair, keratoconus, corneal dystrophy, keratitis, and other related conditions. The aim is to enhance our understanding of the vital role of DNA methylation in the pathogenesis of corneal injuries and the development of cornea-related diseases. The phenomenon of DNA methylation in these conditions may offer new ideas and insights for therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123757"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNX17 knockdown improves post-ischemic angiogenesis via blocking lysosomal dependent VEGFR degradation","authors":"Yang Tang ,&nbsp;Shiqi Tang ,&nbsp;Yue Chen ,&nbsp;Junkai Zhang ,&nbsp;Xueling Yu ,&nbsp;Pingyuan Mao ,&nbsp;Wei Wang ,&nbsp;Junyi Yu ,&nbsp;Feng Wang ,&nbsp;Chunyu Zeng","doi":"10.1016/j.lfs.2025.123739","DOIUrl":"10.1016/j.lfs.2025.123739","url":null,"abstract":"<div><div>The treatment options for critical limb ischemia (CLI) are limited, and existing methods are often ineffective in restoring microvascular blood supply. We recently explored the association of sorting nexin 17 (SNX17) with angiogenesis. Knockdown of SNX17 promotes angiogenesis and increased blood flow in hindlimb from hindlimb ischemia mice, accompanied with a higher limb salvage rate. This phenomenon can be attributed to the critical role of SNX17 in the degradation of some angiogenic factor receptors, including vascular endothelial growth factor receptor (VEGFR). The linkage between VEGFR and SNX17 facilitates its trafficking to lysosomal degradation. In the absence of SNX17, VEGFR accumulates in early endosomes, leading to prolonged and intensified activation, and consequently promoting angiogenesis. The current study shows that SNX17 plays an important role in angiogenesis by regulating the stability of angiogenic factor receptors, such as VEGFR, and presents a new strategy for facilitating tissue repair in ischemic environments.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123739"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}