Experimental cell research最新文献

{"title":"Inhibition of HMGN2 SUMOylation ameliorates atherosclerosis by activating PAX5 expression to induce macrophage M2 polarization","authors":"Xiangkui Wang ,&nbsp;Peipei Wu ,&nbsp;Yadi Shen ,&nbsp;Shiwei Xu ,&nbsp;Qi Wan ,&nbsp;Yongfei Yang","doi":"10.1016/j.yexcr.2025.114709","DOIUrl":"10.1016/j.yexcr.2025.114709","url":null,"abstract":"<div><h3>Background</h3><div>As a core pathological process of cardiovascular disease, atherosclerosis (AS) progression is closely linked to macrophage polarization, yet the mechanisms by which post-translational modifications regulate inflammatory responses in AS remain unclear.</div></div><div><h3>Methods</h3><div>Using oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 foam macrophages and high-fat diet-fed (apolipoprotein E knockout) ApoE^−/− mice, we assessed HMGN2 SUMOylation's role in macrophage M2 polarization. Cell proliferation/migration were analyzed via EdU/Transwell assays; macrophage polarization phenotypes were examined by immunofluorescence. Inflammatory cytokines and NF-κB pathway were quantified using ELISA/Western blot. Aortic plaque formation and lipid deposition were evaluated through HE staining and Oil Red O lipid visualization.</div></div><div><h3>Results</h3><div>In cellular experiments, research demonstrated that HMGN2 enhances interaction with the transcription factor PAX5 through SUMOylation, thereby inhibiting PAX5 activity and driving macrophage polarization toward the pro-inflammatory M1 phenotype. Furthermore, PIAS1 knockdown significantly reduced HMGN2 SUMOylation levels. This disruption suppressed the binding between PAX5 and HMGN2 and reduced inflammatory factor release. Animal experiments revealed that targeted PIAS1 knockdown markedly reduced aortic plaque area, improved lipid metabolic disorders, and modulated inflammatory cytokines by inhibiting NF-κB signaling pathway.</div></div><div><h3>Conclusion</h3><div>The present study systematically reveals the molecular mechanism by which HMGN2 SUMOylation regulates macrophage polarization and inflammatory response through the \"PAX5-NF-κB\" signaling axis, which may become a new target for the treatment of atherosclerosis by targeting epigenetic modification.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114709"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887092","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":"Corrigendum to “Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling” [Exp. Cell. Res. 364(2) (2018)198–207]","authors":"Shaobo Tian ,&nbsp;Jia Hu ,&nbsp;Kaixiong Tao ,&nbsp;Jian Wang ,&nbsp;Yanan Chu ,&nbsp;Jing Li ,&nbsp;Zhibo Liu ,&nbsp;Xueliang Ding ,&nbsp;Luming Xu ,&nbsp;Qilin Li ,&nbsp;Ming Cai ,&nbsp;Jinbo Gao ,&nbsp;Xiaoming Shuai ,&nbsp;Guobin Wang ,&nbsp;Lin Wang ,&nbsp;Zheng Wang","doi":"10.1016/j.yexcr.2025.114655","DOIUrl":"10.1016/j.yexcr.2025.114655","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114655"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505274","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":"Membrane attack complex impairs hepatocyte autophagy in alcohol-related liver disease by regulating the SIRT1-FOXO3 signaling","authors":"Zhigao Hu ,&nbsp;Shanshan Jiang ,&nbsp;Zhen Wan ,&nbsp;Laihui Luo ,&nbsp;Minglong Wang ,&nbsp;Hua Qiu ,&nbsp;Yanqiang Wang ,&nbsp;Yu Liu ,&nbsp;Renfeng Shan","doi":"10.1016/j.yexcr.2025.114713","DOIUrl":"10.1016/j.yexcr.2025.114713","url":null,"abstract":"<div><h3>Background</h3><div>Impaired hepatocyte autophagy is a key feature of alcohol-related liver disease (ALD). Activation of the membrane attack complex (MAC) regulates autophagy. This study examined the role and regulatory mechanisms of MAC in hepatocyte autophagy during ALD progression.</div></div><div><h3>Methods</h3><div>For the animal model, C57BL/6 mice were fed a Lieber-DeCarli liquid diet containing 5 % ethanol (EtOH) (w/v). For the cell model, AML12 cells were exposed to 100 mM EtOH for 72 h. Pathological changes in the liver were examined using hematoxylin–eosin staining, and hepatic steatosis was evaluated using Oil Red O staining. The mRNA and protein expression levels were analyzed by RT-qPCR and western blotting, respectively. Secretion levels of pro-inflammatory cytokines were determined by ELISA. Immunofluorescence staining was employed to detect C5b-9 and LC3 levels, as well as FOXO3 cellular localization. The interaction between FOXO3 and the LAMP2 promoter was analyzed using the ChIP assay.</div></div><div><h3>Results</h3><div>MAC inhibition reduced liver injury, lipid accumulation, and inflammation in the liver tissues of ALD mice while promoting hepatocyte autophagy. CD59 overexpression not only inhibited EtOH-induced lipid accumulation and inflammation in AML12 cells but also promoted autophagy by activating the SIRT1-FOXO3 axis. Mechanistically, SIRT1 promoted FOXO3-mediated LAMP2 transcriptional activation by enhancing the deacetylation and nuclear translocation of FOXO3. As expected, SIRT1 silencing weakened the effects of CD59 overexpression on lipid accumulation, inflammatory response, and autophagy in EtOH-treated AML12 cells.</div></div><div><h3>Conclusion</h3><div>MAC inhibition enhances LAMP2-mediated hepatocyte autophagy in ALD by promoting SIRT1-mediated FOXO3 deacetylation and nuclear translocation, thereby alleviating ALD progression.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114713"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895463","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":"Antagonistic interaction between Notch3 signaling and CREB/KLF15 pathway in regulating the phenotypic alterations of glomerular parietal epithelial cells in adriamycin-induced nephropathy","authors":"Yuqing Zhu ,&nbsp;Kaili Chang ,&nbsp;Ke Sun ,&nbsp;Yifeng Wang ,&nbsp;Zhonghua Zhao ,&nbsp;Qi Chen ,&nbsp;Qiaojing Qin ,&nbsp;Xueguang Liu","doi":"10.1016/j.yexcr.2025.114724","DOIUrl":"10.1016/j.yexcr.2025.114724","url":null,"abstract":"<div><div>Parietal epithelial cells (PECs) that line the Bowman’s capsule are considered progenitor cells for podocytes, which exhibit limited regeneration capacity following injury. Notch3 receptor has been found to be co-expressed in both podocytes and PECs in focal segmental glomerulosclerosis (FSGS), suggesting a distinct regulatory role in this context. Our previous research indicated that Notch3 signaling is significantly negatively correlated with the cAMP-PKA-CREB-KLF15 pathway in adriamycin (ADR)-injured podocytes. Given the common embryonic origin of PECs and podocytes, we hypothesize that Notch3 signaling and CREB-KLF15 pathway may play a critical role in the phenotypic alterations of PECs. We generated Notch3 knockout mice and established ADR-induced nephropathy. Notably, Notch3 knockdown improved both renal function and morphology in middle-aged mice (56–60 weeks) and those with ADR-induced nephropathy. In Notch3^+/− mice, the number of PECs co-expressing podocyte markers was significantly higher compared to that in wild-type mice. In cultured PECs, ADR directly induced phenotypic changes of PECs by modulating Notch3 signaling and CREB-KLF15 pathway. Notch3 overexpression by lentiviral transfection resulted in significant activation of PECs and increased expressions of p-ERK. Furthermore, pCPT-cAMP, a selective activator of cAMP-PKA pathway, or VRAD medium, markedly enhanced CREB-KLF15 pathway and the expressions of podocyte markers. U0126, a specific inhibitor of MEK/ERK, significantly inhibited Notch3 signaling while concurrently increasing the expression of CREB-KLF15. Taken together, these findings suggest that Notch3-p-ERK signaling and CREB-KLF15 pathway exert antagonistic effects in modulating PECs phenotype, with p-ERK potentially serving as a molecular switch in the interaction between these two signaling pathways.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114724"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904177","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 “Silenced long non-coding RNA activated by DNA damage elevates microRNA-495-3p to suppress atherosclerotic plaque formation via reducing Krüppel-like factor 5” [Exp. Cell Res. 401 (2021) 112519]","authors":"Dan-Ni Fu ,&nbsp;Yu Wang ,&nbsp;Li-Jun Yu ,&nbsp;Ming-Jie Liu ,&nbsp;Dong Zhen","doi":"10.1016/j.yexcr.2025.114633","DOIUrl":"10.1016/j.yexcr.2025.114633","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114633"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274550","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":"Corrigendum to ‘Analysis of the in vitro response of the Sapajus cay (Primates: Platyrrhini) genome to exposure to the radiomimetic bleomycin’ [Exp. Cell Res. 450 (2025) 114689]","authors":"Mariela Nieves ,&nbsp;Romina Celeste Páez ,&nbsp;Esteban Orlando Ferreras ,&nbsp;Melina Noelia Ortuño Orgaz ,&nbsp;Nancy Beatriz Andrioli","doi":"10.1016/j.yexcr.2025.114698","DOIUrl":"10.1016/j.yexcr.2025.114698","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114698"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855004","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":"Inhibition of crosstalk between iNKT cells and macrophages mitigates ischemia-reperfusion injury in steatotic livers","authors":"Yu Kuroda ,&nbsp;Yoshiya Ito ,&nbsp;Nobuyuki Nishizawa ,&nbsp;Mina Tanabe ,&nbsp;Atsushi Yamashita ,&nbsp;Kanako Hosono ,&nbsp;Mariko Kamata ,&nbsp;Masashi Satoh ,&nbsp;Yusuke Kumamoto ,&nbsp;Naoki Hiki ,&nbsp;Hideki Amano","doi":"10.1016/j.yexcr.2025.114728","DOIUrl":"10.1016/j.yexcr.2025.114728","url":null,"abstract":"<div><div>Liver ischemia-reperfusion (IR) injury is a substantial form of damage that occurs during liver transplantation and resection surgeries. Steatotic livers are particularly susceptible to IR injury, but few strategies to effectively alleviate this issue in steatotic livers exist. Invariant natural killer T (iNKT) cells regulate IR injury in healthy livers as well as liver repair by interacting with macrophages. In this study, we explored the role of iNKT cell-macrophage crosstalk in IR injury in steatotic livers. High-fat diet (HFD)-fed macrophage-specific CD1d conditional knockout (<em>Cd1d</em>^{<em>△mac</em>}) and Cd1d^flox control (Cont) mice were subjected to liver IR. HFD-fed <em>CD1d</em>^{<em>△mac</em>} mice showed mitigation of IR-induced liver damages with reduction of hepatic necrosis and inflammation along with promotion of liver repair. Flow cytometric analysis revealed that HFD-fed <em>Cd1d</em>^{<em>△mac</em>} mice showed increased hepatic reparative macrophages and interleukin (IL)-13-positive iNKT cells but decreased pro-inflammatory macrophages with IL-1β. IL-13 administration to HFD-fed Cont mice attenuated IR injury and accelerated liver recovery, which was associated with accumulation of hepatic macrophages skewed to a reparative phenotype. IL-13 promoted reparative macrophage polarization in bone marrow (BM)-derived <em>Cd1d</em>-deficient macrophages in vitro. Blockade of IL-13 in HFD-fed <em>Cd1d</em>^{<em>△mac</em>} mice aggravated IR injury. Overall, inhibiting iNKT cell-macrophage crosstalk attenuates steatotic liver IR injury and facilitates liver repair via IL-13-mediated reparative macrophage polarization. These findings provide new insights into therapeutic strategies to regulate the vulnerability of the steatotic liver to IR injury.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114728"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916355","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 “DDX18 influences chemotherapy sensitivity in colorectal cancer by regulating genomic stability” [Exp. Cell Res. 444 (2025) 114344]","authors":"Wenchao Zhao ,&nbsp;Qingqing Luo ,&nbsp;Han Zhan ,&nbsp;Zhen Du ,&nbsp;Tan Deng ,&nbsp;Huaxin Duan","doi":"10.1016/j.yexcr.2025.114559","DOIUrl":"10.1016/j.yexcr.2025.114559","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114559"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274549","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":"Liraglutide ameliorates intrauterine adhesion by inhibiting NF-κb phosphorylation and reducing epithelial-mesenchymal transition","authors":"Jie Shi ,&nbsp;Weicong Xu ,&nbsp;Tao Yang ,&nbsp;Ayana Bayijuma ,&nbsp;Yujie Huang ,&nbsp;Yunxiao Zhou","doi":"10.1016/j.yexcr.2025.114708","DOIUrl":"10.1016/j.yexcr.2025.114708","url":null,"abstract":"<div><h3>Background</h3><div>Intrauterine adhesions (IUA) seriously affect female reproductive function, but the clinical treatment effect is not good. Semaglutide and Dulaglutide, receptor agonists of the gastrointestinal hormone GLP-1, have been reported to alleviate IUA. We sought to determine whether liraglutide, also a GLP-1 receptor agonist, would exert a protective effect and explore the underlying mechanism.</div></div><div><h3>Methods</h3><div>The IUA rat models were conducted via the mechanical damage method and rats were administrated with liraglutide. The inflammation and collagen fibrosis were evaluated via hematoxylin-eosin and Masson staining. The content of E-cadherin and N-cadherin was measured by immunohistochemistry, immunofluorescence, and Western blot. To stimulate IUA, human endometrial organoids were treated with RU486, and primary human endometrial epithelial cells were treated with TGF-β. SuperPred analysis was to predict the potential targets of liraglutide, with cellular thermal shift assay to detect its interaction with NF-κb.</div></div><div><h3>Results</h3><div>Liraglutide treatment reduced endometrial inflammation, collagen fibrosis, and EMT in IUA rats as well as human organoid IUA models. NF-κb phosphorylation was up-regulated in the IUA model group and was reversed by liraglutide treatment. Database predictions suggested that NF-κb may be a predicted direct target of liraglutide and our results confirmed that. Further results showed that in human endometrial organoids, interfering with the targeting of NF-κB by liraglutide attenuated the effects of liraglutide on inflammation, fibrosis, and EMT in the IUA models.</div></div><div><h3>Conclusions</h3><div>Liraglutide reduces EMT by directly targeting NF-κb and inhibiting NF-κb phosphorylation, thereby improving IUA.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114708"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816134","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":"CALD1-derived circ-0003746 targeting miR-526b promotes EMT-mediated bladder cancer progression","authors":"Dengke Yang ,&nbsp;Weipu Mao ,&nbsp;Lei Jiang ,&nbsp;Bingyan Liu ,&nbsp;Jiang Geng","doi":"10.1016/j.yexcr.2025.114710","DOIUrl":"10.1016/j.yexcr.2025.114710","url":null,"abstract":"<div><div>CALD1 is critical to bladder cancer (BCa) development. Circ-0003746 is a circRNA derived from two exons of CALD1. However, the functional role of circ-0003746 in BCa remains inadequately explored. This study investigated its involvement in BCa. Circ-0003746 was found to be overexpressed in BCa tissues and cell lines. Silencing circ-0003746 suppressed both proliferation and migration of BCa cells <em>in vitro</em> and <em>in vivo</em>. miR-526b was identified as a potential target of circ-0003746. Luciferase reporter assays confirmed the interaction between circ-0003746 and miR-526b. Mechanistically, circ-0003746 promotes epithelial-mesenchymal transition (EMT) by sequestering miR-526b, thereby advancing BCa progression. These findings highlight the role of circ-0003746 in regulating the miR-526b/EMT axis, positioning it as a potential biomarker for BCa.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"451 2","pages":"Article 114710"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862233","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}