Experimental cell research最新文献

{"title":"Deduhonghua-7 powder and its bioactive component Luteolin alleviate hepatic fibrosis through CHRM3/NF-κB axis.","authors":"Yumei, Anda, Runguo Xue, HaSi, Tana Bai, Yingchun Bai, Zhiqiang Han","doi":"10.1016/j.yexcr.2026.115169","DOIUrl":"https://doi.org/10.1016/j.yexcr.2026.115169","url":null,"abstract":"<p><strong>Background: </strong>To examine the hepatoprotective and antifibrotic properties of Deduhonghua-7 powder and its active component luteolin in a CCl₄-induced liver fibrosis model, followed by in-depth analysis of the associated molecular mechanisms.</p><p><strong>Methods: </strong>A CCl₄-induced chronic hepatic injury mouse model was constructed to evaluate the therapeutic efficacy of Deduhonghua-7 powder. Potential targets and active components were predicted through network pharmacology and molecular docking, followed by molecular dynamics simulations to verify the binding stability of luteolin to key targets. The antifibrotic mechanism of luteolin was further investigated in CCl₄-stimulated LX2 human hepatic stellate cells and CHRM3-overexpression models.</p><p><strong>Results: </strong>Deduhonghua-7 powder significantly ameliorated CCl₄-induced hepatic histopathological damage, reduced collagen deposition, and normalized serum ALT, AST, and ALP levels. Network pharmacology analysis identified 30 therapeutic targets and revealed multi-component, multi-target mechanisms. Molecular docking and dynamics studies consistently showed stable binding interactions between luteolin and core targets CHRM3 and STAT3, with binding free energies reaching ≤-13.39 kcal/mol. Notably, luteolin treatment markedly restored CHRM3 expression that was suppressed by CCl₄ both in vivo and in vitro. Either CHRM3 activation via oxotremorine-M or CHRM3 overexpression significantly inhibited CCl₄-induced upregulation of α-SMA and COL1A1, mimicking the antifibrotic effects of luteolin. Furthermore, luteolin-mediated CHRM3 restoration contributed to reduced hepatic inflammation, characterized by lower levels of IL-1β, IL-6, and TNF-α, and attenuated NF-κB p65 phosphorylation.</p><p><strong>Conclusion: </strong>Deduhonghua-7 powder exerts potent antifibrotic effects against CCl₄-induced liver injury. Luteolin, a key active component, attenuates hepatic fibrosis and inflammation by upregulating CHRM3 expression, thereby inhibiting hepatic stellate cell activation and NF-κB signaling.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115169"},"PeriodicalIF":3.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896939","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":"Retraction notice to “Tumor necrosis factor α stimulates endothelin-1 synthesis in rat hepatic stellate cells in hepatic wound healing through a novel IKK/JNK pathway” [Exp. Cell Res. 317 (2011) 1040-1048]","authors":"Shuxin Zhan,&nbsp;Don C. Rockey","doi":"10.1016/j.yexcr.2026.115130","DOIUrl":"10.1016/j.yexcr.2026.115130","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"462 1","pages":"Article 115130"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629922","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":"METTL3-mediated m⁶A Modification Exacerbates Vascular Endothelial Inflammation in Coronary Artery Disease by Regulating DNMT1 mRNA Stability.","authors":"JiuMao Ye, PeiChao Ren, RenJie Song","doi":"10.1016/j.yexcr.2026.115167","DOIUrl":"https://doi.org/10.1016/j.yexcr.2026.115167","url":null,"abstract":"<p><p>Chronic vascular endothelial inflammation plays a pivotal role in the pathogenesis of coronary artery disease (CAD). N⁶-methyladenosine (m⁶A), the predominant epitranscriptomic modification in messenger RNA (mRNA), regulates pro-atherogenic inflammatory responses in coronary endothelial cells. This study explores the role of the m⁶A methyltransferase METTL3 in CAD-associated endothelial inflammation through its regulation of DNA methyltransferase 1 (DNMT1) mRNA stability. Using cultured human coronary artery endothelial cells (HCAECs), an apolipoprotein E-deficient (ApoE^-/^-) mouse model of atherosclerosis, and clinical atherosclerotic specimens from CAD patients, a marked increase in METTL3 expression was observed in CAD endothelium and within plaques. METTL3 knockdown strongly suppressed tumor necrosis factor-α (TNF-α)-induced expression of pro-inflammatory mediators interleukin-6 (IL-6) and interleukin-1β (IL-1β), while upregulating anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10). Mechanistically, METTL3 bound to and deposited m⁶A modifications in the 3' untranslated region (3'UTR) of DNMT1 mRNA, thereby enhancing its association with the m⁶A reader protein YTH N6-methyladenosine RNA binding protein 1 (YTHDF1). This interaction increased DNMT1 mRNA stability and elevated its protein levels. Furthermore, endothelial-specific Mettl3 deletion significantly reduced aortic atherosclerotic lesion area and inflammatory infiltration in ApoE^-/^- mice. In summary, METTL3-mediated m⁶A modification promotes DNMT1 expression by stabilizing its mRNA, thereby aggravating vascular endothelial inflammation in CAD. The METTL3-m⁶A-DNMT1 axis may represent a potential therapeutic target for CAD.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115167"},"PeriodicalIF":3.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864431","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":"Role of the MALAT1-Importin 7-HIF1A regulatory axis in the progression of cutaneous squamous cell carcinoma.","authors":"Ying Zhang, Lijun Feng, Xing Mi, Jiacheng Li, Huimin Zhang, Lu Wang, Lin Xiao, Meijuan Zhou","doi":"10.1016/j.yexcr.2026.115158","DOIUrl":"10.1016/j.yexcr.2026.115158","url":null,"abstract":"<p><p>Ultraviolet-B radiation is a major environmental factor contributing to the development of cutaneous squamous cell carcinoma (cSCC). In our previous study, we found that UVB exposure induces the expression of the long non-coding RNA (lncRNA) MALAT1 in HaCaT cells, and that MALAT1 promotes cSCC progression. In the present study, we observed that MALAT1 regulates the expression of the nuclear transporter protein Importin 7 (IPO7) in human cSCC. Both in vitro and in vivo experiments showed that IPO7 plays a pro-tumorigenic role in cSCC by promoting cell proliferation, migration, and invasion, and by inhibiting apoptosis. Furthermore, an interaction between IPO7 and HIF1α (HIF1A) was identified; silencing IPO7 impaired the nuclear import of HIF1α and reduced its transcriptional activity. Mechanistically, we found that MALAT1 co-binds with the transcription factor c-MYC at the IPO7 promoter to regulate IPO7 expression. Collectively, our data suggest that the MALAT1-IPO7-HIF1α axis may promote the malignant behaviors of cSCC cells and contribute to cSCC progression.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115158"},"PeriodicalIF":3.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864402","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":"AMPK-YAP/TAZ signaling pathway mediates the amelioration of endothelial dysfunction elicited by moderate-intensity exercise-induced wall shear stress.","authors":"Yanxia Wang, Yanyan Sun, Peng Shen, Wen Zhang, Wenxuan Pan, Xinchen Zhang, Zhaoxia Xu, Xiumei Guan, Yiying Sun, Min Cheng","doi":"10.1016/j.yexcr.2026.115168","DOIUrl":"10.1016/j.yexcr.2026.115168","url":null,"abstract":"<p><strong>Background: </strong>Arterial endothelial dysfunction is a critical early pathological change in cardiovascular diseases. Exercise-induced wall shear stress (WSS) exerts protective effects on impaired arterial endothelial function, while the underlying mechanism remains unclear. YAP/TAZ are core mechanotransduction molecules. This study aims to investigate whether YAP/TAZ mediate the ameliorative effect of moderate intensity exercise (MIE)-induced WSS on endothelial dysfunction via AMPK regulation.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS)-injured HUVECs were exposed to MIE-induced WSS using a multicomponent parallel-plate flow chamber system. SiRNA-mediated knockdown of AMPK and YAP was performed to verify the regulatory signaling pathway. In vivo, high-fat diet ApoE^-/- mice received MIE intervention to assess the impacts of MIE on endothelial function and YAP expression.</p><p><strong>Results: </strong>LPS induced YAP/TAZ activation and endothelial dysfunction, whereas MIE-induced WSS inhibited YAP/TAZ activation and reversed endothelial dysfunction in LPS-treated cells. YAP knockdown strengthened the ameliorative effect of MIE-induced WSS on endothelial dysfunction. Furthermore, AMPK knockdown promoted YAP activation and attenuated the beneficial impact of MIE-induced WSS on endothelial dysfunction. Consistently, MIE intervention reversed high-fat diet-induced impairment of common carotid arterial endothelial function, concurrent with YAP downregulation in vivo. These results indicate that MIE-induced WSS ameliorates endothelial dysfunction via activating AMPK, which in turn inhibits YAP/TAZ.</p><p><strong>Conclusions: </strong>This study provides novel insights into the molecular mechanism by which MIE-induced WSS alleviates endothelial dysfunction, and provides a theoretical foundation for the clinical application of MIE as a rehabilitation strategy to improve impaired arterial endothelial function.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115168"},"PeriodicalIF":3.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857125","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":"Squalene epoxidase in cancer: Mechanistic insights, therapeutic potential, and future perspectives.","authors":"Qingxin Zhang, Chunhui Zhang, Dabin Liu","doi":"10.1016/j.yexcr.2026.115166","DOIUrl":"10.1016/j.yexcr.2026.115166","url":null,"abstract":"<p><p>Metabolic reprogramming is a hallmark of malignancy. SQLE, a key regulated enzyme catalyzing the first oxygen-dependent step of cholesterol biosynthesis downstream of canonical HMG-CoA reductase, is aberrantly upregulated across multiple human malignancies and drives tumor progression and therapeutic resistance. This review examines the emerging role of SQLE as a potential metabolic-immune checkpoint, systematically integrating cutting-edge epitranscriptomic regulatory mechanisms published from 2024 to 2026, dissecting the full spectrum of SQLE-mediated immunosuppressive pathways, and conducting critical comparative analysis between repurposed antifungal SQLE agents and novel mammalian-selective inhibitors to advance combinatorial immunotherapy strategies. Beyond summarizing canonical transcriptional, post-transcriptional and post-translational cascades governing SQLE cholesterol homeostasis, we elaborate how SQLE reshapes membrane lipid signaling, sustains cancer stem cell stemness, facilitates epithelial-mesenchymal transition, and triggers redox and epigenetic remodeling to fuel malignant phenotypes. We further thoroughly unpack three interconnected immunosuppressive axes orchestrated by SQLE: oxysterol-driven myeloid-derived suppressor cell recruitment, stabilized PD-L1 palmitoylation mediating T cell exhaustion, and squalene depletion-triggered persistent NF-κB inflammatory signaling, which collectively lock tumors into an immune-excluded \"cold\" state in selected preclinical models. We objectively dissect the pharmacokinetic bottlenecks limiting terbinafine's single-agent anti-tumor efficacy and discuss the developmental advantages and toxic challenges of human-specific SQLE inhibitors. Finally, we highlight unresolved research gaps, prioritize translational directions including SQLE expression as a potential biomarker for immunotherapy responsiveness requiring independent cohort validation, the development of low-toxicity selective SQLE degraders, and synergistic regimens combining SQLE blockade with immune checkpoint inhibitors or ferroptosis inducers, offering a comprehensive and critical update for lipid metabolism and tumor immunology researchers.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115166"},"PeriodicalIF":3.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849915","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":"IRF8 transcriptionally drives NAIP to promote NLRP3/NLRC4 inflammasome-mediated renal tubular pyroptosis in diabetic kidney disease.","authors":"Xiaorong Zou, Rui Su, Xueyan Liang, Xiaoling Wang, Ming Zhang, Wei Jin, Xing Li, Chunli Mei, Fang Li, Wei Guo, Jie Li","doi":"10.1016/j.yexcr.2026.115155","DOIUrl":"10.1016/j.yexcr.2026.115155","url":null,"abstract":"<p><strong>Objective: </strong>Renal tubular pyroptosis is a key driver of inflammation and fibrosis in diabetic kidney disease (DKD), yet the contribution of the NAIP-NLRC4 inflammasome arm and its upstream transcriptional control have remained undefined. This study investigated whether NAIP causally promotes tubular pyroptosis in DKD and identified the transcription factor responsible for its induction.</p><p><strong>Methods: </strong>NAIP and IRF8 expression were examined across Nephroseq DKD cohorts and correlated with renal function. Naip1-6^Δ/Δ and Irf8-knockout mice, together with high glucose-treated HK-2 cells, were used to assess pyroptosis and fibrosis. IRF8 binding to the NAIP promoter was tested by JASPAR prediction, chromatin immunoprecipitation and dual-luciferase reporter assays, and causality was confirmed by NAIP knockdown/overexpression and by AAV9-mediated NAIP restoration in Irf8-knockout mice.</p><p><strong>Results: </strong>NAIP was upregulated in diabetic renal tissue and correlated with declining renal function. Naip deletion attenuated proteinuria, fibrosis and NLRP3/NLRC4-dependent pyroptosis in STZ-diabetic mice, and NAIP knockdown reproduced this protection in high glucose-treated HK-2 cells. IRF8 was concurrently induced under hyperglycemia and correlated with NAIP expression; IRF8 bound directly to the NAIP promoter and transcriptionally activated it. NAIP overexpression abolished the protective effects of IRF8 silencing in vitro, and AAV9-mediated NAIP restoration similarly reversed the renoprotection conferred by Irf8 knockout in vivo.</p><p><strong>Conclusion: </strong>IRF8 transcriptionally drives NAIP expression to promote tubular inflammasome activation, pyroptosis and fibrosis in DKD, establishing the IRF8-NAIP axis as a novel mechanistic link and candidate therapeutic target in diabetic kidney disease.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115155"},"PeriodicalIF":3.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790195","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":"FAM117B Promotes Malignant Progression of Hepatocellular Carcinoma by Forming a Bidirectional Regulatory Loop with NAT10 and Activating the JAK-STAT3 Pathway.","authors":"Zhaohong Wang, Jian Fang, Lijun Wu, Xinchang Zhang, Zihao Xu, Xiangyang Xue, Zhengfei Wang, Yunfeng Shan","doi":"10.1016/j.yexcr.2026.115151","DOIUrl":"https://doi.org/10.1016/j.yexcr.2026.115151","url":null,"abstract":"<p><p>HCC (Hepatocellular carcinoma) is one of the malignant tumors with high morbidity and mortality worldwide. Its pathogenesis is complex and the efficacy of existing treatments is limited. Therefore, in-depth exploration of key regulatory molecules and their mechanisms is of great significance for the early diagnosis and targeted therapy of HCC. In this study, HCC cell lines Huh-7 and HepG2 were used as research models to systematically investigate the biological function and molecular regulatory mechanism of FAM117B (family with sequence similarity 117 member B) in HCC progression through gene knockdown and overexpression, cell functional assays, co-immunoprecipitation coupled with mass spectrometry, post-translational modification detection, transcriptome sequencing and nude mouse subcutaneous tumorigenesis assays. High FAM117B expression predicted poor prognosis and positively correlated with pathological grade; functionally, FAM117B exhibited robust oncogenic activity, where its knockdown suppressed proliferation, clonogenicity, invasion, and migration, and its overexpression enhanced these phenotypes. Mechanistic studies revealed that FAM117B directly physically interacted with NAT10 (N-acetyltransferase 10), an acetyltransferase, forming a bidirectional regulatory loop: on the one hand, FAM117B maintained the protein stability of NAT10 by inhibiting its K48-linked ubiquitination and subsequent proteasomal degradation; on the other hand, NAT10, as a key acetyltransferase, specifically mediated the acetylation of FAM117B at lysine 429, providing a molecular basis for the functional role of FAM117B. Transcriptome sequencing and molecular verification demonstrated that the FAM117B/NAT10 axis targeted and regulated JAK2 (Janus kinase 2) expression, activated the downstream JAK-STAT3 (signal transducer and activator of transcription 3) signaling pathway, and thereby drove the malignant biological behaviors of HCC cells. In vivo, dual knockdown of FAM117B and NAT10 significantly reduced xenograft growth, decreased Ki67, and increased apoptosis; notably, NAT10 depletion abrogated the tumor-promoting effects of FAM117B overexpression. In conclusion, this study reveals the molecular mechanism by which FAM117B promotes HCC progression via forming a bidirectional regulatory loop with NAT10 and activating the JAK-STAT3 signaling pathway through acetylation modification, providing a novel potential target and theoretical basis for targeted therapy of HCC.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"115151"},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759364","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":"Role of CIRP in glioma Progression: Inhibition of ferroptosis via UBR5-Mediated ACSL4 degradation","authors":"Zhiyin Pang ,&nbsp;Xingwang Zu ,&nbsp;Ying Yang ,&nbsp;Pingping Yan ,&nbsp;Huicong Wang ,&nbsp;Junjie Liu ,&nbsp;Jinmin Hao","doi":"10.1016/j.yexcr.2026.114942","DOIUrl":"10.1016/j.yexcr.2026.114942","url":null,"abstract":"<div><div>Glioma represents the most aggressive form of primary brain tumor, characterized by restricted therapeutic strategies and unfavorable survival rates. Accumulating studies indicate that ferroptosis is critically involved in the advancement of glioma. Although cold-inducible RNA-binding protein (CIRP), an RNA chaperone protein, upregulated in various malignancies, has not been thoroughly investigated in glioma. This research revealed that CIRP is a significantly upregulated gene in glioma patients, with high expression correlating with worse prognosis. Through functional experiments, we demonstrated that CIRP enhances proliferative, migratory, and invasive capacities of glioma cells. Notably, we discovered that CIRP enhanced GBM cell resistance to ferroptosis, as evidenced by reduced intracellular iron levels, decreased lipid peroxidation, and elevated antioxidant capacity. Mechanistic studies revealed that CIRP facilitated the interaction between the E3 ubiquitin ligase UBR5 and ACSL4, leading to increased ubiquitination and subsequent proteasomal degradation of ACSL4. In summary, our findings indicate that CIRP advances glioma progression via inhibiting ferroptosis through the promotion of UBR5-mediated ACSL4 degradation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 2","pages":"Article 114942"},"PeriodicalIF":3.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194346","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":"Temporal modulation of cuproptosis and autophagy mediates nanographene-driven pulmonary fibrosis progression","authors":"Jiarui Xia ,&nbsp;Xiaolong Tang ,&nbsp;Huijie Shang ,&nbsp;Youliang Zhao ,&nbsp;Shuqi Li ,&nbsp;Ke Tang ,&nbsp;Yi Li ,&nbsp;Wenzhuo Wu ,&nbsp;Qun Xu ,&nbsp;Changfu Hao ,&nbsp;Wu Yao","doi":"10.1016/j.yexcr.2026.114927","DOIUrl":"10.1016/j.yexcr.2026.114927","url":null,"abstract":"<div><div>Graphene nanoparticles are increasingly used in materials manufacturing, pollutant treatment, energy storage, and electronic devices, and the potential risk of occupational and environmental exposure is a concern. The mechanisms of lung fibrosis induced by nano-graphene with different properties are complex. In addition, multiple modes of programmed cell death (PCD) occur during lung fibrosis, and whether cuproptosis and autophagy exert regulatory effects during the progression of lung fibrosis induced by nano-graphene remains undocumented. In this study, we constructed mouse models with varying doses of graphene and exposure durations. We observed the dynamics of pathological changes in lung histology and the time-series expression of biomarkers. We discovered that graphene could deposit in lung tissue, leading to the pathological manifestations of pulmonary fibrosis; this was coincident with elevated copper ion concentration, cellular cuproptosis, and excessive autophagy. In short, our results may contribute to further elucidation of the potential respiratory toxic effects and mechanisms of graphene, and to the early development of targeted preventive and control measures by providing new ideas and reference points.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"457 1","pages":"Article 114927"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122739","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}