Molecular immunology最新文献

{"title":"Corrigendum to “Regulation of macrophage pyroptosis by SIRT1 during Pseudomonas aeruginosa-induced pneumonia” (Mol. Immunol. 185 (2025) 7110)","authors":"Haibo Ding , Xinzhu Xiao , Yuping Zhan , Yanqing Lin , Changsheng Xu , Yiming Zeng","doi":"10.1016/j.molimm.2025.09.007","DOIUrl":"10.1016/j.molimm.2025.09.007","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Page 254"},"PeriodicalIF":3.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK upregulates SOCS1 to promote TFEB nuclear transfer, enhances autophagy, inhibits macrophage M1 polarization and relieves acute lung injury","authors":"Wensha Nie ,&nbsp;Chuxiong Gong ,&nbsp;Yongze Liu,&nbsp;Jiawu Yang,&nbsp;Qinglang Dai,&nbsp;Yuan Liao,&nbsp;Feng Li","doi":"10.1016/j.molimm.2025.10.002","DOIUrl":"10.1016/j.molimm.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Acute lung injury (ALI) is a life-threatening inflammatory disease. Macrophage polarization plays a key role in the occurrence of pulmonary inflammation. Therefore, regulating the phenotype of macrophages is a potentially effective method for the treatment of ALI. This study aims to explore the potential molecular mechanism of SOCS1 in M1 polarization of macrophages and ALI.</div></div><div><h3>Methods</h3><div>The ALI animal model was established by intratracheal infusion of LPS (5 mg/kg), and the cell model was established by stimulating RAW264.7 macrophages with LPS (1 μg/mL). The levels of autophagy and macrophage markers were detected by immunofluorescence, MDC staining, western blot. ELISA was used to measure the levels of inflammatory cytokines. The level of MPO in the lungs was determined, and inflammatory cells and proteins in BALF were detected.</div></div><div><h3>Results</h3><div>The expressions of SOCS1, TFEB and p-AMPK decreased in the ALI model. Overexpression of SOCS1 inhibited the M1 polarization of macrophages induced by LPS, reduced the expressions of pro-inflammatory factors IL-1β, IL-6 and TNF-α, increased the expression of anti-inflammatory factor IL-10, and decreased the expressions of iNOS, CD80 and CD86, and increase the expressions of Arg1, CD206 and CD163. Further studies have revealed that SOCS1 activates autophagy by up-regulating the expression of TFEB, thereby inhibiting the polarization of M1 in macrophages. Furthermore, SOCS1 can promote the nuclear translocation of TFEB, while the phosphorylation of AMPK can up-regulate SOCS1 to promote the expression of TFEB.</div></div><div><h3>Conclusion</h3><div>AMPK promotes nuclear transfer of TFEB by up-regulating SOCS1, thereby enhancing autophagy and inhibiting M1 polarization in macrophages, thus alleviating ALI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 240-253"},"PeriodicalIF":3.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of efferocytosis in liver transplantation via hepatic macrophage","authors":"Minjie Zhao ,&nbsp;Xuesong Xu ,&nbsp;Haiyang Peng ,&nbsp;Changlin Tang ,&nbsp;Jiefu Luo ,&nbsp;Junyan Liu ,&nbsp;Zuojin Liu ,&nbsp;Jianping Gong ,&nbsp;Junhua Gong ,&nbsp;Jinzheng Li","doi":"10.1016/j.molimm.2025.10.003","DOIUrl":"10.1016/j.molimm.2025.10.003","url":null,"abstract":"<div><div>Liver transplantation has undergone progressive advancements since the 1960s, with optimized surgical techniques and improved outcomes resulting from standardized procedures and therapeutic regimens. However, postoperative complications—such as ischemia-reperfusion injury, acute rejection, hepatocellular carcinoma recurrence, and biliary injury—continue to significantly affect both survival rates and quality of life in liver transplant recipients. Efferocytosis, the phagocytic clearance of apoptotic cells, plays a critical role in preventing necrosis-induced inflammation and promoting tissue resolution and repair. Accumulating evidence suggests that impaired efferocytosis is associated with several complications following liver transplantation. Although multiple hepatic cell types participate in efferocytosis, macrophages—notably Kupffer cells and monocyte-derived macrophages—are the primary mediators responsible for clearing apoptotic cells in the liver. Nevertheless, significant gaps remain in our understanding of how hepatic macrophages perform efferocytosis and whether defects in this process within donor-derived macrophages exacerbate post-transplant complications. This review provides a comprehensive discussion of efferocytosis, with a focus on its impact on liver transplantation-related complications. Furthermore, we explore the potential of targeting efferocytosis as a novel therapeutic strategy in liver transplantation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 221-228"},"PeriodicalIF":3.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolic regulation of tumor-associated macrophage reprogramming","authors":"Hao Fan ,&nbsp;Dongxiao Lu ,&nbsp;Xianyong Yin ,&nbsp;Hao Sun ,&nbsp;Zhihai Wang ,&nbsp;Haohan Sun ,&nbsp;Xiangyin Liu ,&nbsp;Yuming Li ,&nbsp;Zijian Zhou ,&nbsp;Liang Chen ,&nbsp;Yinyan Wang ,&nbsp;Tao Xin","doi":"10.1016/j.molimm.2025.10.006","DOIUrl":"10.1016/j.molimm.2025.10.006","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) are an essential component of the immune cells that infiltrate the tumor microenvironment (TME) and exhibit immunosuppressive functions. These macrophages exhibit significant phenotypic plasticity and heterogeneity, highlighting their capacity to adapt to various environmental signals. This adaptability facilitates polarization shifts between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. As tumors proliferate and metastasize, the TME progressively transforms into an immunosuppressive environment. Consequently, TAMs undergo metabolic reprogramming in pathways such as glucose, lipid, and amino acid metabolism, among others, which ultimately drive the establishment of an immunosuppressive phenotype. While TAMs do not strictly conform to the M1 and M2 classifications, they often exhibit characteristics resembling M2 macrophages, thereby promoting tumor growth via immunosuppression. This review aims to elucidate the metabolic reprogramming of TAMs and investigate how they maintain their immunosuppressive phenotype, highlighting potential avenues for metabolic therapies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 198-209"},"PeriodicalIF":3.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GATA1 promotes TGF-β1-induced epithelial-mesenchymal transition by regulating GSDMB in human bronchial epithelial cells","authors":"Jiao-jiao Li ,&nbsp;Jia-he Chen ,&nbsp;Yue Yuan ,&nbsp;Ling Li ,&nbsp;Chen Zhou ,&nbsp;Hu Chen ,&nbsp;Jia Geng ,&nbsp;Qian Cao ,&nbsp;Rui Jin","doi":"10.1016/j.molimm.2025.10.004","DOIUrl":"10.1016/j.molimm.2025.10.004","url":null,"abstract":"<div><div>Asthma is a common inflammatory airway disorder characterized by recurrent cough, chest tightness, and dyspnea. The repeated inflammation of bronchial epithelial cells leading to epithelial-mesenchymal transition is believed to play a pivotal role in airway remodeling associated with asthma. Gasdermin B (GSDMB), a member of the gasdermin family of structurally related proteins, has been identified as having a strong association with asthma. However, the precise role of GSDMB in asthma pathophysiology remains ambiguous. This study aimed to elucidate the biological function of GSDMB in asthma and its upstream regulatory mechanisms. Our findings demonstrated that GSDMB expression was also increased in human bronchial epithelial cells stimulated with transforming growth factor-β1 (TGF-β1). Overexpression of GSDMB resulted in an upregulation of intermediate mesenchymal markers following TGF-β1 treatment, thereby facilitating epithelial-mesenchymal transition (EMT) processes. Furthermore, GSDMB enhanced both proliferation and migration capacity in TGF-β1-treated Beas-2B cells. Notably, the transcription factor GATA1 was found to bind to the promoter region of GSDMB and facilitate its expression levels. These results indicate that the transcriptional axis involving GATA1/GSDMB exerts functions promoting EMT along with enhancing cellular proliferation and migration within TGF-β1-stimulated bronchial epithelial cells; suggesting that targeting GSDMB may represent a viable therapeutic strategy for managing asthma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 229-239"},"PeriodicalIF":3.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosgenin ameliorates CLP-induced sepsis in mice via suppressing inflammatory responses and preserving intestinal mucosal barrier integrity","authors":"Yuanyuan Li ,&nbsp;Jiajia Zeng ,&nbsp;Xuan Zhong ,&nbsp;Qiting Huang ,&nbsp;Xianfei Wang ,&nbsp;Shuya Sun ,&nbsp;Huamin Wang ,&nbsp;Xiaoqi Huang ,&nbsp;Jiajun Ling ,&nbsp;Rongfeng Lin","doi":"10.1016/j.molimm.2025.10.005","DOIUrl":"10.1016/j.molimm.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Diosgenin, a well-known steroid sapogenin, has demonstrated anti-inflammatory effects; however, its therapeutic potential for sepsis remains unclear. Intestinal barrier dysfunction is a critical contributor to lethal sepsis, a systemic inflammatory response syndrome. This study investigated the protective effects of diosgenin on cecal ligation and puncture (CLP)-induced sepsis in mice, focusing on its impact on intestinal mucosal dysfunction and inflammation. Additionally, the effects of diosgenin on the expression of the endogenous antimicrobial peptide mCRAMP and the TLR4/MyD88 signaling pathway were investigated.</div></div><div><h3>Methods</h3><div>Sepsis was induced in male C57BL/6 mice via CLP. Survival rates were recorded, and serum and ileum tissue levels of TNF-α and IL-6 were quantified to assess the protective efficacy of diosgenin treatment. Intestinal barrier integrity was evaluated by hematoxylin and eosin (H&amp;E) staining, while mucosal permeability was determined using serum D-lactic acid. Tight junction (TJ) proteins were detected via Western blotting. Immunohistochemistry was used to measure mCRAMP protein expression in the ileum, and quantitative real-time PCR (qRT-PCR) was employed to analyze the gene expression of mCRAMP, TLR4, and MyD88. Molecular docking was performed with Autodock4 software to predict the binding capacity between diosgenin and LL-37, TLR4 and MyD88.</div></div><div><h3>Results</h3><div>Diosgenin treatment significantly improve the survival of mice, decreased TNF-α and IL-6 production, and attenuated intestinal histopathological damage. Additionally, diosgenin decreased serum D-lactic acid levels, upregulated Claudin-1 and Occludin expression, and increased both mRNA and protein levels of mCRAMP while downregulating the gene expression of TLR4 and MyD88. Molecular docking analysis demonstrated favorable binding affinities of diosgenin to LL-37 (−6.3 kcal/mol), TLR4 (−8.3 kcal/mol), and MyD88 (−10.5 kcal/mol). All calculated binding energies were &lt; −5.0 kcal/mol, suggesting potential effective binding of diosgenin to these targets.</div></div><div><h3>Conclusion</h3><div>Diosgenin improved survival, suppressed inflammatory responses, and preserving intestinal mucosal barrier integrity in CLP-induced septic mice. These protective effects might involve alterations in mCRAMP expression and TLR4/MyD88 signaling.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 210-220"},"PeriodicalIF":3.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody preparation and immunological analysis of RBD from the SARS-CoV-2 Omicron BF.7 variant","authors":"Quansheng Wang ,&nbsp;Chenyi Wang ,&nbsp;Zhicheng Zhang ,&nbsp;Siyu Fan ,&nbsp;Ping Lei ,&nbsp;Shiguo Liu ,&nbsp;Mingzhi Li ,&nbsp;Keyi Wang ,&nbsp;Yanni Zhang ,&nbsp;Lumei Kang ,&nbsp;Shiqi Weng ,&nbsp;Lingbao Kong ,&nbsp;Ting Wang","doi":"10.1016/j.molimm.2025.09.008","DOIUrl":"10.1016/j.molimm.2025.09.008","url":null,"abstract":"<div><div>The SARS-CoV-2 spike protein facilitates target recognition, cellular entry, and viral infection, leading to varying degrees of COVID-19 severity. Amino acid site mutations in the S protein RBD region can enhance the spread and immune evasion of the SARS-CoV-2 Omicron variant. The study aimed to construct a prokaryotic expression vector for the S protein RBD of the SARS-CoV-2 Omicron BF.7 variant strain. <em>Escherichia coli</em> was used to express the RBD protein, and a polyclonal antibody was generated to investigate the immunological functions of the Omicron (BF.7) RBD. Optimization of expression conditions in <em>Escherichia coli</em> was conducted to achieve stable expression of pET-28a-BF.7-RBD, including induced temperature, induced time, and IPTG concentration. Serum antibody titers in RBD-immunized mice reached up to 1: 204800 as determined by indirect enzyme-linked immunosorbent assay. The polyclonal antibody could detect prokaryotic and eukaryotic RBD proteins, as well as commercial RBD proteins, and splenocytes were found to produce high levels of IFN-γ. This study successfully demonstrated the production of a large quantity of RBD protein with strong immunogenicity in <em>E. coli</em>, eliciting robust humoral and cellular immune responses in mice. The generation of high-potency polyclonal antibodies provides valuable insights for further research on the biological functions of the RBD protein, detection of Omicron variants, and vaccine development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 188-197"},"PeriodicalIF":3.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma","authors":"Paula Gršković ,&nbsp;Valentino Mihalić ,&nbsp;Anja Krstulović ,&nbsp;Peter Möller ,&nbsp;Suzana Hančić ,&nbsp;Slavko Gašparov ,&nbsp;Petra Korać","doi":"10.1016/j.molimm.2025.09.009","DOIUrl":"10.1016/j.molimm.2025.09.009","url":null,"abstract":"<div><h3>Objectives</h3><div>Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as <em>cREL</em> and <em>PD-L1</em>, whose expression is also influenced by cytokines TNF-α and IFN-γ.</div></div><div><h3>Methods</h3><div>In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of <em>cREL</em>, <em>CXCL10</em> and <em>PD-L1</em> expression. Additionally, the expression of <em>TNF-α</em>, <em>IFN-γ</em>, <em>cREL</em>, <em>CXCL10</em>, <em>CXCR3</em>, <em>PD-L1</em> and <em>PD-1</em> genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils.</div></div><div><h3>Results</h3><div>Prolonged exposure to TNF-α increased <em>cREL</em> expression, while IFN-γ strongly induced <em>CXCL10</em> expression. The change in the expression of <em>PD-L1</em> in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples.</div></div><div><h3>Conclusions</h3><div>the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 178-187"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1PR2-miR-212 feedback loop regulates allergic reactions","authors":"Jaewhoon Jeoung,&nbsp;Hyein Jo,&nbsp;Wonho Kim,&nbsp;Dooil Jeoung","doi":"10.1016/j.molimm.2025.10.001","DOIUrl":"10.1016/j.molimm.2025.10.001","url":null,"abstract":"<div><div>We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions <em>in vitro</em> and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions <em>in vitro</em>. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 166-177"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCBP2 alleviates myocardial infarction by inhibiting cardiomyocyte ferroptosis via the NDUFS1/NRF2 pathway.","authors":"Qianrong Zhang, Aiping Jin, Haijuan Cheng, Yuanyuan Zheng, Bing Li","doi":"10.1016/j.molimm.2025.08.002","DOIUrl":"10.1016/j.molimm.2025.08.002","url":null,"abstract":"<p><strong>Background: </strong>Poly(C) binding protein 2 (PCBP2) was reported to alleviate cardiomyocyte damage, but its molecular mechanism remains unclear. The current study aimed to investigate the role and potential mechanism of PCBP2 in progression of MI.</p><p><strong>Methods: </strong>An in vivo MI model was established by ligation of the left anterior descending (LAD) branch in mice. PCBP2 expression was detected in Normal and MI groups. H9C2 cells were treated with OGD for 0, 2, 4, and 6 h to screen for optimal time to establish MI model in vitro. H9C2 cells were transfected with pcDNA-PCBP2, and the effect of PCBP2 overexpression on OGD-induced oxidative stress, inflammation and ferroptosis was evaluated. Subsequently, the interaction of PCBP2 with NDUFS1 mRNA was predicted by the Starbase database and verified by RNA-immunoprecipitation (RIP) and RNA-protein pull-down assay. Next, a series of reversal experiments were performed to verify the regulation of PCBP2 on NDUFS1 expression. Then, pcDNA-NDUFS1 was transfected into H9C2 and MIND4-17 (NRF2 protein activator) treated for reversal experiments to assess the effect of NDUFS1 on NRF2-mediated ferroptosis. Finally, LV-PCBP2 and LV-NDUFS1 lentiviral vectors were intrapericardially injected into MI mice, and the role of PCBP2 and NDUFS1 in the progression of MI was verified in vivo.</p><p><strong>Results: </strong>PCBP2 was downregulated in MI model and OGD-induced H9C2 cells. PCBP2 improved cell proliferation and inhibited oxidative stress, inflammation and ferroptosis in OGD-incubated H9C2 cells. PCBP2 bound with NDUFS1 mRNA and promoted NDUFS1 expression in H9C2 cells, which promoted NRF2 activation by enhancing NRF2 nuclear translocation and inhibited NRF2-mediated ferroptosis. Finally, administration of LV-PCBP2 and LV-NDUFS1 alleviated myocardial tissue injury and MI infarct in mice through suppressing cardiomyocyte ferroptosis and inflammation.</p><p><strong>Conclusion: </strong>Our results suggested that PCBP2 alleviated MI by inhibiting cardiomyocyte ferroptosis through interacting with NDUFS1 mRNA and activating NRF2-Keap1 pathway.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"13-25"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}