Experimental cell research最新文献

{"title":"Mulberry leaf flavonoid extract inhibits high glucose-induced ferroptosis by regulating the PI-3K/Akt/Nrf2/GPX4 pathway in HT22 mouse hippocampal neuronal cells","authors":"Fan Yang ,&nbsp;Liang Li ,&nbsp;Tao Chai ,&nbsp;Han Xu ,&nbsp;Yue Zhang ,&nbsp;Li Zhou ,&nbsp;JiaoJiao Huang ,&nbsp;Yan Jiang","doi":"10.1016/j.yexcr.2025.114848","DOIUrl":"10.1016/j.yexcr.2025.114848","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the inhibitory effects of mulberry leaf flavonoid extract (MFE) on high glucose-induced diabetic encephalopathy (DE) in a cell model, and to investigate the underlying mechanisms combined with network pharmacology prediction and experimental validation.</div></div><div><h3>Methods</h3><div>A DE cell model was established by chronic high glucose stimulation of HT22 mouse hippocampal neuronal cells. Following intervention with MFE, cell viability, advanced glycation end products (AGEs) content, and ferroptosis-related indices were detected. Network pharmacology was used to screen potential signaling pathways and key targets of MFE, while Western blotting validated the expression of proteins related to the screened pathways and targets.</div></div><div><h3>Results</h3><div>Network pharmacology screening identified Akt1, ALB, TNF, IL-1B, and IL-6 as the top-ranked targets. Molecular docking confirmed stable binding between major MFE components and these potential targets. MFE treatment markedly upregulated ferritin heavy chain (FTH) and ferroportin (FPN) levels while decreasing transferrin receptor (TFRC) levels, attenuating iron overload in DE cells. It also suppressed AGEs accumulation, which activated the downstream PI3K/Akt/Nrf2/SLC7A11/GPX4 ferroptosis regulatory pathway to mitigate oxidative stress and inhibit ferroptosis. Additionally, MFE activated Akt, leading to p38 MAPK deactivation, reduced Bax/Bcl-2 ratio, and decreased Caspase-3 levels, blocking the apoptosis pathway. It alleviated inflammatory injury by suppressing the p38 MAPK/NF-κB pathway, thereby reducing TNF-α, IL-1β, and IL-6 protein levels.</div></div><div><h3>Conclusion</h3><div>MFE inhibits ferroptosis by upregulating the PI3K/Akt/Nrf2/GPX4 signaling pathway. This study provides valuable insights into the therapeutic application of MFE for DE.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114848"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microRNA-100 inhibits cell division in human non-small cell lung cancer via a CDC25A signaling mechanism","authors":"Mo Xu ,&nbsp;Zhijun Chen ,&nbsp;Fan Yang ,&nbsp;Siying Wang","doi":"10.1016/j.yexcr.2025.114846","DOIUrl":"10.1016/j.yexcr.2025.114846","url":null,"abstract":"<div><div>Lung cancer is one of the most common malignancies worldwide, and the prognosis remains unsatisfactory with conventional treatments. Our research revealed that miR-100 is significantly decreased in non-small cell lung cancer (NSCLC) tissues and cell lines, indicating its potential role in NSCLC development. The upregulation of miR-100 expression inhibited the growth of L18 NSCLC cells, while its downregulation increased the growth of A549 NSCLC cells. Cell cycle dysregulation is a key factor in NSCLC development. CDC25A is a vital cell cycle regulator that promotes cell cycle progression. Our objective was to determine the function of the CDC25A protein and its effect on the prognosis of NSCLC patients. The luciferase reporter gene assay demonstrated direct targeting of the 3′ non-coding sequence of CDC25A by miR-100-3p. Western blot analysis confirmed that the protein expression levels of cyclin D1, CDK6, pRb, and E2F3 decreased upon miR-100 overexpression. Furthermore, cell cycle analysis demonstrated that miR-100 overexpression led to G1 phase arrest and a concomitant reduction in S phase entry in NSCLC cells. <em>In vivo</em> studies using a xenograft mouse model demonstrated that miR-100 overexpression inhibited tumor growth, while its inhibition accelerated it. Rescue experiments confirmed that CDC25A partially reversed the cell cycle arrest and growth suppression mediated by miR-100. This study's findings suggest that miR-100 can inhibit NSCLC progression by specifically targeting CDC25A, a cell cycle regulator, and its downstream molecular targets. Hence, miR-100 may have significant therapeutic potential against NSCLC.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114846"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Aurora B inhibitor ZM-447439 induces caspase-independent necrosis-like death in v-Src oncogene-expressing cells via accumulation of extra-lysosomal cathepsin B","authors":"Taishi Josen ,&nbsp;Ryuzaburo Yuki ,&nbsp;Youhei Saito ,&nbsp;Takuya Honda ,&nbsp;Shuhei Soeda ,&nbsp;Yuji Nakayama","doi":"10.1016/j.yexcr.2025.114840","DOIUrl":"10.1016/j.yexcr.2025.114840","url":null,"abstract":"<div><div>Src signaling is aberrantly activated in various cancers, and therapeutic strategies targeting Src-dependent cancers have been developed. We previously reported that cells expressing the oncogenic mutant v-Src are resistant to microtubule-targeting agents (MTAs), yet paradoxically exhibiting sensitivity to the Aurora B inhibitor ZM-447439; however, the mechanism underlying this cytotoxicity remains unclear. In this study, we demonstrate that the Aurora B inhibitor ZM-447439 potentiates cell death in v-Src-expressing HeLa S3 and HCT116 cells, accompanied by the accumulation of tetraploid and polyploid cells. The pan-caspase inhibitor z-VAD-FMK treatment does not affect the cell death. Time-lapse imaging analysis reveals cell death with the feature of necrosis in ZM-447439-treated v-Src expressing cells: altered morphology and loss of membrane integrity without chromatin condensation. Although autophagic flux is impaired, the autophagosome accumulation does not contribute to cell death. Notably, the cathepsin B expression is elevated in v-Src-expressing cells, and the amount of mature active cathepsin B outside lysosomes is strongly increased upon ZM-447439 treatment in v-Src-expressing cells. Treatment with the cathepsin B inhibitor CA-074 methyl ester mitigates cell death, similar to the pan-cysteine cathepsin inhibitor E64d treatment. These results suggest that the Aurora B inhibitor ZM-447439 potentiates caspase-independent necrosis-like death in v-Src-expressing cells partly through the accumulation of extra-lysosomal cathepsin B. The Aurora B inhibitors might be promising therapeutic agents for Src-driven cancers.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114840"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-124–3p suppresses lung cancer by targeting ITGB1/PI3K/p-AKT signal transduction pathway","authors":"Ruiyun Han ,&nbsp;Shunjuan Wang ,&nbsp;Zhen Zhou ,&nbsp;Dengliang Huang ,&nbsp;Jing Hou ,&nbsp;Meiyuan Tian ,&nbsp;Rili Ge ,&nbsp;Yanyan Ma","doi":"10.1016/j.yexcr.2025.114852","DOIUrl":"10.1016/j.yexcr.2025.114852","url":null,"abstract":"<div><div>Worldwide, lung cancer is a leading cause of cancer-related death, and non-small cell lung cancer (NSCLC) represents the most common histological subtype. Numerous studies have demonstrated that microRNAs (miRNAs) play critical roles in NSCLC pathogenesis. microRNA-124–3p (miR-124–3p) has been identified as a tumor-associated miRNA, and we confirmed its downregulation in NSCLC cells. Functional assays showed that overexpression of miR-124–3p suppresses proliferation and migration of NSCLC cells, whereas its knockdown promotes these malignant phenotypes. A luciferase reporter assay revealed that miR-124–3p directly targets ITGB1 by binding to its 3′-UTR. Mechanistically, ITGB1 enhances PI3K expression and increases AKT phosphorylation, thereby activating the PI3K/AKT signaling pathway. Notably, miR-124–3p retained its tumor-suppressive effects even in A549 cells engineered to express the PIK3CA^H1047L mutation. Consistent with this, bioinformatics analysis demonstrated that miR-124–3p expression is significantly lower in tumor tissues than in adjacent normal lung and further decreases in advanced T stage (T3–T4) compared to early stage (T1–T2). These findings indicate that miR-124–3p inhibits NSCLC progression via the ITGB1/PI3K/p-AKT axis and remains functional despite PIK3CA activation, supporting its potential as a therapeutic candidate.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114852"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin inhibits heterotopic ossification of mouse Achilles tendon by inhibiting the Nr4a1/Wnt/β-catenin signaling pathway","authors":"Danxia Zheng ,&nbsp;Mengyu Jiang ,&nbsp;Wenjie Wang ,&nbsp;Jianglin Yu ,&nbsp;Xiaoyang Qi ,&nbsp;Yixin Chen","doi":"10.1016/j.yexcr.2025.114824","DOIUrl":"10.1016/j.yexcr.2025.114824","url":null,"abstract":"<div><div>Heterotopic ossification is a pathological process characterized by aberrant bone formation in soft tissues, leading to joint pain, stiffness, functional impairment, and poor quality of life. We used a mouse Achilles tendon heterotopic ossification model and in vitro tendon-derived stem cells (TDSCs) assays to identify the molecular mechanism of metformin in prevention of heterotopic ossification. Metformin significantly attenuated heterotopic ossification, reducing ectopic bone volume and osteogenic gene expression. In vitro, metformin inhibited TDSCs osteogenic differentiation in a dose-dependent manner, decreasing calcium nodule deposition and osteogenic marker expression. Transcriptomic analysis revealed downregulated Nr4a1 expression in metformin-treated heterotopic ossification samples; in vitro experiments confirmed that Nr4a1 activation enhances TDSCs osteogenesis, and Nr4a1 knockdown suppresses osteogenesis. Metformin also reduced Wnt4 and β-catenin expression, suggesting that Nr4a1 promotes heterotopic ossification by positively regulating Wnt/β-catenin signaling. In sum, metformin downregulates expression of Nr4a1 in TDSCs, which suppresses osteogenic differentiation by inhibiting Wnt/β-catenin signaling. As a mediator of TDSC osteogenic differentiation, Nr4a1 may be a therapeutic target for heterotopic ossification.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114824"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudane V alleviates ox-LDL-induced macrophage M1 polarization by inhibiting m6A modification of PPARGC1A","authors":"Tao Li ,&nbsp;Qi Pang ,&nbsp;Jun Pan ,&nbsp;Ya Gao ,&nbsp;Yuan Huang ,&nbsp;Wei Tian ,&nbsp;Junchuan Ran ,&nbsp;Zheng Zhu ,&nbsp;Yongbin Liu ,&nbsp;Kunsheng Li","doi":"10.1016/j.yexcr.2025.114842","DOIUrl":"10.1016/j.yexcr.2025.114842","url":null,"abstract":"<div><div>Atherosclerosis is driven by oxidized low-density lipoprotein (ox-LDL)-triggered macrophage malfunction, yet the precise pathways and effective counter-measures remain elusive. Here we delineated how N6-methyladenosine (m⁶A) RNA methylation governs ox-LDL-induced M1 macrophage polarization and evaluated marine natural products for therapeutic intervention. Human monocytic THP-1 cells differentiated into M0 macrophages were treated with ox-LDL. M1/M2 polarization states were analyzed using flow cytometry, and changes in polarization markers were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Global m6A changes were detected using m⁶A dot blot and quantification analysis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed to identify downstream target genes of the ox-LDL-m⁶A pathway. The role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) in ox-LDL-induced M1 polarization was analyzed. A high-throughput marine natural product library was employed to discover agents capable of reversing ox-LDL-driven macrophage polarization. ox-LDL induces macrophage M1 polarization, and M1 macrophages damage endothelial cells. ox-LDL-induced polarization of macrophages into the M1 phenotype was associated with increased global RNA m⁶A modification. High levels of m⁶A modification induced by ox-LDL suppressed PPARGC1A expression in a YTH domain family 2 (YTHDF2)-dependent manner, leading to M1 polarization. Pseudane V, a marine natural product, effectively reduced ox-LDL-induced M1 polarization and protected vascular endothelial cells by correcting abnormal m⁶A modification of PPARGC1A. In conclusion, ox-LDL induces m⁶A modification of PPARGC1A, suppressing its expression and promoting M1 polarization of macrophages, contributing to atherosclerosis development. Pseudane V counteracts excessive m⁶A modification caused by ox-LDL, preventing M1 polarization of macrophages. These findings suggest the potential use of Pseudane V in preventing atherosclerosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114842"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone H3 lysine 18 lactylation promotes alveolar epithelial cell apoptosis in sepsis-induced lung injury by upregulating caspase-8 in vivo and in vitro","authors":"Ping Lin ,&nbsp;Yu Wang ,&nbsp;Xiaoqian Li ,&nbsp;Zongan Liang ,&nbsp;Ting Wang","doi":"10.1016/j.yexcr.2025.114843","DOIUrl":"10.1016/j.yexcr.2025.114843","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is a leading cause of acute lung injury (ALI), with apoptosis of alveolar epithelial cells (AECs) playing a central role. Elevated lactate, a hallmark of sepsis-induced metabolic reprogramming, has recently been implicated in lysine lactylation. However, its contribution to AEC apoptosis and ALI pathogenesis remains unclear.</div></div><div><h3>Methods</h3><div>A cecal ligation and puncture (CLP) mouse model and LPS-stimulated AECs were used to investigate the role of lysine lactylation in AEC apoptosis. Histopathological analysis, western blotting, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, chromatin immunoprecipitation (ChIP) assays, and pharmacological interventions with Oxamate, recombinant TNF-α, and the caspase-8 inhibitor Z-IETD-FMK were performed.</div></div><div><h3>Results</h3><div>Compared with sham controls, septic mice exhibited significantly elevated lactate levels, enhanced inflammation, increased pulmonary apoptosis, and aggravated lung injury. Both septic lung tissues and LPS-stimulated AECs showed significant upregulation of pan-lysine lactylation (pan-Kla) and histone H3 lysine 18 lactylation (H3K18la). ChIP analysis showed that H3K18la was highly enriched in the caspase-8 promoter region. Consistently, lactate exposure increased caspase-8 expression, which potentiated TNF-α-induced apoptosis in AECs. Pharmacological inhibition of lactate production or caspase-8 activity significantly alleviated pulmonary apoptosis and lung injury in septic mice.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that lactate-driven H3K18la promotes TNF-α-induced AEC apoptosis by upregulating caspase-8 in sepsis-induced ALI. Targeting this lactate/H3K18la/caspase-8 axis may represent a promising therapeutic strategy for sepsis-induced ALI.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 2","pages":"Article 114843"},"PeriodicalIF":3.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAM10 promotes uveal melanoma development by regulating the wnt/β-catenin pathway","authors":"Xiaolan Yang,&nbsp;Fangju Han,&nbsp;Yuanyuan Guo,&nbsp;Xin Zhang","doi":"10.1016/j.yexcr.2025.114522","DOIUrl":"10.1016/j.yexcr.2025.114522","url":null,"abstract":"<div><h3>Background</h3><div>Uveal melanoma (UVM) seriously affects people's health and quality of life. Here, the mechanism of a disintegrin and metallopeptidase domain 10 (ADAM10) was elucidated in UVM.</div></div><div><h3>Methods</h3><div>The clinical prognosis and potential biological function of ADAM10 gene in UVM patients were assessed using a series of bioinformatics methods. RT-qPCR and Western blot assay were employed to detect genes expression. Cell apoptosis and viability were examined by flow cytometry, clone formation and CCK-8 assays. The migrated and invasive abilities were analyzed by wound healing and transwell assays. Tumor growth was performed in Xenograft mouse model.</div></div><div><h3>Results</h3><div>We found that ADAM10 expression was significantly associated with poor prognosis of UVM patients, and its prognostic significance for UVM patients was determined by distinct clinical characteristics. In vitro, ADAM10 expression was upregulated in MUM-2B and C918 UVM cell lines. More importantly, ADAM10 downregulation discouraged cell viability, metastasis but triggered apoptosis of UVM cells. Moreover, ADAM10 upregulation can promote the tumor growth of UVM <em>in vivo</em>. Mechanically, ADAM10 downregulation blocked the Wnt/β-catenin pathway in UVM.</div></div><div><h3>Conclusion</h3><div>Downregulation of ADAM10 discourages the malignant behaviors of UVM through inhibiting the Wnt/β-catenin pathway.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 1","pages":"Article 114522"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin produces therapeutic effects against preeclampsia by activating Wnt 3a signaling and inhibiting ferroptosis","authors":"Qiang Xu ,&nbsp;Ge Xuan ,&nbsp;Chongying Zhu ,&nbsp;Bingquan Zhu ,&nbsp;Zihao An ,&nbsp;Meiyuan Jin ,&nbsp;Chao Tang","doi":"10.1016/j.yexcr.2025.114827","DOIUrl":"10.1016/j.yexcr.2025.114827","url":null,"abstract":"<div><div>Preeclampsia (PE) is a multisystem disorder with increased maternal and perinatal mortality and morbidity while the treatment of PE remains largely unknown in clinic. Therefore, it is necessary to find more effective therapeutic methods of PE. We report herein that, Tianma Gouteng Decoction (TGD) generates protective effects against PE by activating Wnt 3a/β-catenin signaling and simultaneously suppressing ferroptosis in placental trophoblast cells. Particularly, Gastrodin (Gtd), the active component in TGD, plays a major role in protection against PE. Mechanistically, Gtd up-regulates the Wnt 3a/β-catenin signaling activity by inducing <em>Wnt 3a</em> mRNA expression, resulting in the increased expression of β-catenin-controlled target genes. On the other hand, Gtd-triggered Wnt activation obviously exerts negative effects on ferroptosis by promoting expression levels of the anti-ferroptosis proteins accompanied by the down-regulated reactive oxygen species (ROS) production and total iron content but the up-regulated L-Glutathione (GSH) levels. Consistently, Gtd-administration reveals apparent anti-hypertensive effects in a PE-like mouse model with diminished ferroptosis, whereas deactivation of β-catenin by administration with the specific antagonist ICG001 disrupts the protective effects derived from Gtd. Therefore, our results provide an innovative basis for the role of Gtd as a new therapy for PE.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 1","pages":"Article 114827"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANXA1 inhibits ferroptosis in HUVECs via negative regulation of ferritinophagy","authors":"Jingjing Wang ,&nbsp;Jinqiu Jia ,&nbsp;Zitong Cao ,&nbsp;Zeming Cai ,&nbsp;Kai Zhang ,&nbsp;Jin He ,&nbsp;Chunyan Wu ,&nbsp;Zuo Wang","doi":"10.1016/j.yexcr.2025.114825","DOIUrl":"10.1016/j.yexcr.2025.114825","url":null,"abstract":"<div><div>Ferroptosis is a phospholipid peroxidation-mediated and iron-dependent cell death form. Inhibiting ferroptosis is a promising strategy for the prevention and treatment of cardiovascular diseases. Annexin A1 (ANXA1) is an endogenous anti-inflammatory mediator that plays an important regulatory role in cardiovascular diseases such as atherosclerosis, especially in inflammation suppression, protecting the heart from injury, and regulating vascular function. Ac2-26 is a synthetic peptide derived from the N-terminal 26 amino acids of ANXA1, which retains its anti-inflammatory properties. However, the regulatory mechanism of ANXA1 in atherosclerosis (AS) is not yet fully understood. This study aims to explore the specific role of ferroptosis in HUVECs and demonstrate that ANXA1 can disrupt ferritinophagy and protect endothelial function. Treatment with Ac2-26 or ANXA1-overexpressing HUVECs alleviated RSL3-induced endothelial cell dysfunction and inhibited lipid peroxidation, as evidenced by a reduction in ferrous ion levels and upregulation of GPX4, FTH1, and SLC7A11 protein expression, along with a downregulation of LC3-II and NCOA4 expression. In contrast, knockdown of ANXA1 in HUVECs failed to suppress the outcome of ferroptosis. Furthermore, co-immunoprecipitation analysis revealed that ANXA1 overexpression prevented ferritin degradation by disrupting the NCOA4-FTH1 protein-protein interaction, reducing the bioavailability of intracellular ferrous ions, thereby blocking ferroptosis. In conclusion, our findings identify a novel mechanism, showing that ANXA1 can inhibit ferroptosis via ferritinophagy, thereby alleviating endothelial dysfunction, which may provide a new therapeutic avenue for AS.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"454 1","pages":"Article 114825"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}