Redox Biology最新文献

{"title":"SERPINE1 drives ferroptosis in acute respiratory distress syndrome by disrupting mitochondrial NAD+ homeostasis and suppressing Sirt3 activity","authors":"Nan Gao, Wei-Jian Zhang, Yi-Xin Qian, Song Yang, Zheng-Nan Zhang, Hao-Tian Lu, Guo-Qiang Zhang","doi":"10.1016/j.redox.2026.104146","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104146","url":null,"abstract":"Acute Respiratory Distress Syndrome (ARDS) is characterized by alveolar epithelial injury, inflammatory dysregulation, oxidative stress, and impaired repair capacity. Ferroptosis, an iron-dependent and lipid peroxidation–driven form of regulated cell death, has emerged as a pathogenic driver of ARDS; however, the upstream molecular regulators that initiate ferroptotic signaling in alveolar epithelial cells remain poorly defined. SERPINE1 (PAI-1), a mediator of inflammation, coagulation dysfunction, and epithelial injury, is frequently elevated in sepsis and ARDS, yet its mechanistic role in ferroptosis remains unknown.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"423 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147736450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRF2 controls a diverse network of antiviral effectors with p62 acting as a central restriction factor effective across virus families","authors":"Alice Pedersen ,&nbsp;Julia Blay-Cadanet ,&nbsp;Jacob Storgaard ,&nbsp;Bruno Hernaez ,&nbsp;Jacob Thyrsted ,&nbsp;Cecilie S. Bach-Nielsen ,&nbsp;Krishna Twayana ,&nbsp;Sofie E. Jørgensen ,&nbsp;Clàudia Rio-Bergé ,&nbsp;Cecilie Poulsen ,&nbsp;Anne L. Thielke ,&nbsp;Emil A. Thomsen ,&nbsp;Joanna Kalucka ,&nbsp;David Olagnier ,&nbsp;Yonglun Luo ,&nbsp;Fulvio Reggiori ,&nbsp;Trine H. Mogensen ,&nbsp;Antonio Alcamí ,&nbsp;Anne Louise Hansen ,&nbsp;Christian K. Holm","doi":"10.1016/j.redox.2026.104135","DOIUrl":"10.1016/j.redox.2026.104135","url":null,"abstract":"<div><div>The transcription factor erythroid 2 (NFE2)-related factor 2 (NRF2) is a key regulator of cellular homeostasis. Recent discoveries have identified agonists of NRF2 as inducers of broad cellular resistance to viral infection including SARS-CoV-2. Nevertheless, it is still unclear to what extent NRF2 itself is an inducer of anti-viral immunity and its downstream antiviral effectors have not been mapped. Here, we first demonstrate through specific genetic activation and silencing that NRF2 restricts SARS-CoV-2 replication. We then used a focused CRISPR-activation screen to map antiviral NRF2-inducible effector genes that restrict replication of SARS-CoV-2, Influenza A virus (IAV), Herpes Simplex virus 1 (HSV1) and Vaccinia virus (VACV). This approach allowed us to identify a range of antiviral effectors each of which restrict members of one or more virus families. Importantly, we identified the NRF2-inducible selective autophagy receptor p62/SQSTM1 as a broadly effective restriction factor across all the tested viruses. Importantly, p62 inhibited SARS-CoV-2 replication in cells treated with the lysosomal inhibitor bafilomycin A1, as well as in cells deficient in the autophagy protein ATG5. Similarly, p62 inhibited replication of HSV1 and IAV independently of ATG5 and ATG16L1 respectively.</div><div>Thus, NRF2 restricts viral replication through a hitherto underappreciated network of antiviral restriction factors effective across multiple virus families. Importantly, we identify p62 as a broadly acting antiviral effector that restricts viral replication independently of canonical autophagy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"93 ","pages":"Article 104135"},"PeriodicalIF":11.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRF2: Master regulator of cellular homeostasis and therapeutic vulnerability in cancer","authors":"Wei-tai Chen ,&nbsp;Nicholas W. McKee ,&nbsp;Damaris Kuhnell ,&nbsp;Matthew Dodson","doi":"10.1016/j.redox.2026.104050","DOIUrl":"10.1016/j.redox.2026.104050","url":null,"abstract":"<div><div>The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is best known for its regulation of the antioxidant response. However, its mediation of other pathways, including key aspects of metabolic and protein homeostasis, has continued to emerge. Accompanying this emergence is an evolved understanding that NRF2 induction across different disease contexts can be beneficial or detrimental depending on the length of activation. This has played an important role in progressing the field forward, as inducing NRF2 is not always the best course of action, and inhibition has gained traction as a viable strategy for treating cancer and other pathologies where NRF2 is chronically active. Despite its rapid growth and a wealth of experimental promise, a persistent shortcoming in the field is a lack of NRF2-specific therapeutics used in clinic. Thus, despite recent advances, there is still room for progress in translating experimental evidence into therapeutic reality. In this review, we will provide a summary of NRF2 regulation and an update on its expanded network of downstream transcriptional programs. We will also discuss targeting NRF2 in disease, focusing on intervention versus prevention depending on the pathological context. Finally, we will briefly highlight current limitations in the field, as well as ongoing approaches that show promise for finally targeting this critical cascade in patient populations.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104050"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serinc2-STAT3 protects against doxorubicin-induced cardiotoxicity via promoting mitochondrial bioenergetics","authors":"Shan Hu ,&nbsp;Manqi Yang ,&nbsp;Tao Liu ,&nbsp;Min Huang ,&nbsp;Hao Ju ,&nbsp;Zheyu Liu ,&nbsp;Saeed Kashkooli ,&nbsp;Mian Cheng ,&nbsp;Gang Wu","doi":"10.1016/j.redox.2026.104045","DOIUrl":"10.1016/j.redox.2026.104045","url":null,"abstract":"<div><h3>Objective</h3><div>Doxorubicin (DOX) is a highly effective anthracycline chemotherapy drug that is commonly used in clinical practice. Because of the accumulation of its drug concentration, their clinical use is associated with severe cardiotoxicity. Serine incorporator 2 (Serinc2) had been shown to play an important role in maintaining cell structure and function. Here, the main purpose of this study was to explore the effect of Serinc2 on doxorubicin-induced cardiotoxicity and its mechanism.</div></div><div><h3>Methods</h3><div>Global Serinc2 knockout (Serinc2-KO) and cardiac-specific Serinc2 overexpression mice received a single or repeated DOX injection to establish chronic cardiotoxicity. Cardiac function, oxidative damage, cell apoptosis, and mitochondrial profiles were evaluated. Transcriptome and co-immunoprecipitation analysis were used to screen the underlying molecular pathways. Neonatal rat ventricle cardiomyocytes (NRVMs) were cultured to elucidate the role and mechanism of Serinc2 in vitro.</div></div><div><h3>Results</h3><div>Our data revealed significantly down-regulated Serinc2 expression in DOX-induced mouse hearts and NRVMs. Serinc2-KO aggravated, while cardiac-specific Serinc2 overexpression alleviated DOX-related myocardial injury, oxidative damage, cell apoptosis, and mitochondrial damage. Mechanistically, Serinc2 deficiency resulted in the impairment of mitochondrial bioenergetics and oxidative phosphorylation in DOX cardiotoxicity. Proteomic profiling and interactome analyses revealed that Serinc2 interacted with STAT3 to increase its phosphorylation and nuclear accumulation, a key factor to regulate mitochondrial bioenergetics. Cardiac overexpression of Serinc2 improves mitochondrial bioenergetics in DOX cardiomyopathy both in vivo and in vitro.</div></div><div><h3>Conclusion</h3><div>Taken together, it can be concluded that Serinc2 can maintain mitochondrial dynamics and increase mitochondrial bioenergy generation by enhancing STAT3 phosphorylation activity, thereby alleviating oxidative stress, apoptotic responses, and improving doxorubicin-induced cardiac dysfunction.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104045"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myo1f regulates monocyte adhesion and contributes to atherosclerosis via MRTFA-dependent ITGB2 expression","authors":"Yifei Lv,&nbsp;Xiaomin Jiang,&nbsp;Yu Chang,&nbsp;Rongrong Huang,&nbsp;Yunwei Chen,&nbsp;Yunfei Deng,&nbsp;Yue Gu,&nbsp;Shaoliang Chen,&nbsp;Linlin Zhu","doi":"10.1016/j.redox.2026.104049","DOIUrl":"10.1016/j.redox.2026.104049","url":null,"abstract":"<div><h3>Background</h3><div>Monocyte adhesion to vascular endothelial cells is a critical step in the pathogenesis of atherosclerosis. While unconventional myosins are known to participate in various cellular activities, their specific role in monocyte-endothelium adhesion remains unclear.In the present study, we investigated the effects of Myosin IF (Myo1f), a class I unconventional myosin, on atherosclerosis and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>A high-cholesterol diet was administered to apolipoprotein E-KO (<em>Apoe</em>^{<em>−/−</em>}) mice to establish an atherosclerosis model, which was further combined with Myo1f knockout to investigate the specific role of Myo1f in atherosclerosis development. Bone marrow transplantation was conducted to assess the significance of Myo1f in myeloid cells related to atherosclerosis. Peripheral blood mononuclear cells (PBMCs) from patients with non-coronary artery disease (non-CAD) and coronary artery disease (CAD) were isolated to examine the correlation between Myo1f and human atherosclerosis. Co-immunoprecipitation mass spectrometry analysis was performed to identify molecules associated with Myo1f, which were subsequently validated and mechanistically investigated through both in vivo and in vitro experiments. Additionally, potential therapeutic drugs for atherosclerosis were explored using the <em>Apoe</em>^{<em>−/−</em>} mouse model.</div></div><div><h3>Results</h3><div>Myo1f expression was found to be significantly increased in PBMCs of patients with coronary artery disease. Moreover, Myo1f-deficient mice exhibited a notable reduction in atherosclerotic plaque area and lipid deposition compared to <em>Apoe</em>^{<em>−/−</em>} mice. Notably, monocyte Myo1f deletion obviously reduced its integrin β2 (ITGB2) expression, consequently impeding the adhesion of monocytes to vascular endothelial cells. Mechanistically, Myo1f promoted actin polymerization by recruiting epithelial protein lost in neoplasm (EPLIN) and depolymerization of G-actin/myocardin-related transcription factor A (MRTFA), leading to the nuclear translocation of MRTFA and upregulation of ITGB2 transcriptional expression. Treatment with CCG-1423, a MRTFA inhibitor, resulted in reduced atherosclerotic lesions in <em>Apoe</em>^{<em>−/−</em>} mice.</div></div><div><h3>Conclusions</h3><div>Our data indicate that Myo1f regulates monocyte adhesion and contributes to the pathogenesis of atherosclerosis by recruiting EPLINα, which stabilizes F-actin. This stabilization enhances MRTFA nuclear translocation, thereby promoting ITGB2 transcription.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104049"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructose-sweetened beverages induce diurnal redox dysregulation in pediatric MASLD","authors":"Helaina E. Huneault ,&nbsp;Scott E. Gillespie ,&nbsp;Zachery R. Jarrell ,&nbsp;Shasha Bai ,&nbsp;Ana Ramirez Tovar ,&nbsp;Cristian Sanchez-Torres ,&nbsp;Lucia A. Gonzalez-Ramirez ,&nbsp;Kelsey C. Chatman ,&nbsp;Thomas R. Ziegler ,&nbsp;Dean P. Jones ,&nbsp;Jean A. Welsh ,&nbsp;Miriam B. Vos","doi":"10.1016/j.redox.2026.104012","DOIUrl":"10.1016/j.redox.2026.104012","url":null,"abstract":"<div><h3>Background</h3><div>Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) redox couples undergo diurnal variation in adults and are more oxidized in obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). There is limited research on redox in children and no data on redox responses to sugars, despite high sugar consumption in this population. This study aimed to describe the diurnal variation of redox couples in children, assess the impact of MASLD, and evaluate responses to fructose versus glucose beverages.</div></div><div><h3>Methods</h3><div>In a 2-day randomized, controlled, crossover feeding study, 26 children (12 with MASLD, 14 controls; aged 10–18 years) consumed isocaloric meals with fructose beverages (FB) on one day and glucose beverages (GB) (set as control) on another, following a washout period. Blood was collected every 2 h over 24 h and analyzed for Cys/CySS and GSH/GSSG. Redox potentials, E_h(Cys/CySS) and E_h(GSH/GSSG), were calculated using the Nernst equation. Linear mixed models assessed diurnal variation and effects of MASLD and beverage type.</div></div><div><h3>Results</h3><div>Plasma E_h(GSH/GSSG) and E_h(CyS/CySS) varied significantly over time after both FB and GB (p &lt; 0.05). With FB, E_h(GSH/GSSG) was significantly more oxidized in children with MASLD (p = 0.034); this was not observed with GB. Among children with MASLD, FB also led to greater E_h(GSH/GSSG) oxidation and lower GSH levels overnight (p &lt; 0.05). While E_h(Cys/CySS) showed a similar trend, differences did not reach statistical significance.</div></div><div><h3>Conclusions</h3><div>Our findings demonstrate that plasma redox states vary diurnally in children and are more oxidized in those with MASLD. Fructose intake increased oxidation of the GSH/GSSG redox couple and lowered GSH concentrations overnight, indicating heightened oxidative stress. These results identify fructose as a driver of redox imbalance in pediatric MASLD and support fructose reduction and glutathione restoration as therapeutic targets.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104012"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical thioredoxin Patrx2 enhances alginate production in mucoid Pseudomonas aeruginosa","authors":"Marie M. Grandjean,&nbsp;James N. Sturgis,&nbsp;Edwige B. Garcin,&nbsp;Moly Ba,&nbsp;Olivier Bornet,&nbsp;Christophe Bordi,&nbsp;Latifa Elantak,&nbsp;Corinne Sebban-Kreuzer","doi":"10.1016/j.redox.2026.104010","DOIUrl":"10.1016/j.redox.2026.104010","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em>, an opportunistic human pathogen, is known for its ability to respond and adapt to its environment, employing intricate adaptation mechanisms that can lead to the formation of complex biofilms. Redox processes play a pivotal role in bacterial adaptation mechanisms. The cytoplasm of most organisms is recognized for maintaining a reducing environment through thiol-disulfide oxidoreductases. In <em>Pseudomonas aeruginosa</em>, we have identified an unusual cytoplasmic thioredoxin named Patrx2. What sets Patrx2 apart is its active site, which contains a consensus sequence, CGHC, identical to the characteristic motif of protein disulfide isomerases (PDIs) found in eukaryotic cells. Our investigations have unveiled that Patrx2, unlike canonical thioredoxins, exhibits disulfide isomerase activity <em>in vitro</em> and displays physicochemical properties, as well as a structural conformation of its catalytic site, reminiscent of PDIs. Using a mutant transposon library, we found that the expression of <em>patrx2</em> is regulated by the alternative sigma factor AlgU, which is implicated in the formation of alginate biofilms in <em>P. aeruginosa</em>. We further demonstrated strong <em>patrx2</em> expression in a mucoid strain we constructed, carrying the clinically relevant <em>mucA22</em> mutation frequently found in cystic fibrosis patients. Furthermore, our results showed a significant decrease in alginate synthesis in a <em>patrx2</em> mutant in this mucoid strain, this effect was also observed in the C34S catalytic variant, suggesting a role for Patrx2's catalytic site in this phenotype. The study of Patrx2, an atypical thioredoxin expressed within an alginate biofilm, underscores the importance of redox regulation in adaptation mechanisms. The induction of Patrx2's expression in alginate-producing biofilms highlights its potential relevance in redox-regulated adaptation mechanisms.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104010"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 “Prevention of colitis-induced liver oxidative stress and inflammation in a transgenic mouse model with increased omega-3 polyunsaturated fatty acids” [Redox Biol. 64 (2023) 102803]","authors":"Nadine Rohwer ,&nbsp;Julia Jelleschitz ,&nbsp;Annika Höhn ,&nbsp;Daniela Weber ,&nbsp;Anja A. Kühl ,&nbsp;Chaoxuan Wang ,&nbsp;Rei-Ichi Ohno ,&nbsp;Nadja Kampschulte ,&nbsp;Anne Pietzner ,&nbsp;Nils Helge Schebb ,&nbsp;Karsten-H. Weylandt ,&nbsp;Tilman Grune","doi":"10.1016/j.redox.2026.104064","DOIUrl":"10.1016/j.redox.2026.104064","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104064"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-specific Angiogenin-mediated tRNA fragments (tDRs) biogenesis shapes the mitochondrial stress response","authors":"Shadi Al-Mesitef ,&nbsp;Daisuke Ando ,&nbsp;Tomoya Saigasaki ,&nbsp;Yuki Sakaguchi ,&nbsp;Shunya Akagi ,&nbsp;Abdulrahman Mousa ,&nbsp;Sherif Rashad ,&nbsp;Kuniyasu Niizuma","doi":"10.1016/j.redox.2026.104038","DOIUrl":"10.1016/j.redox.2026.104038","url":null,"abstract":"<div><div>Transfer RNA-derived small RNAs (tDRs) are emerging regulators of cellular stress response, yet their biogenesis and activities during mitochondrial dysfunction remain poorly understood. Here we profiled tDRs generated in HEK293T cells exposed to inhibitors of respiratory complexes I–V (rotenone, TTFA, antimycin A, KCN, oligomycin) or to arsenite and assessed the impact of CRISPR-mediated angiogenin (ANG) knockout, ANG over-expression and recombinant ANG supplementation on the stress response and tDRs production. tDR-seq revealed stress-specific, highly ordered tDR repertoires: rotenone and antimycin predominantly induced internal (i-tRF) and 3ʹ tRNA (tRF3) fragments, whereas arsenite induced anticodon-cleaved tRNA halves (tiRNAs). mito-tDRs were mostly internal fragments and antimycin induced the strongest mitochondrial tDRs expression. ANG deletion markedly impaired stress-induced tDR biogenesis and sensitized cells to antimycin and oligomycin stress, whereas its overexpression selectively enhanced tDR biogenesis and conferred protection against these mitochondrial stressor. Synthetic tDR mimics failed to rescue viability, implying that native modification patterns or cooperative tDR pools are required. tDR motif enrichment analysis identified YBX1-binding sites among antimycin-induced tDRs, and genetic perturbation of YBX1 phenocopied aspects of enhanced mitochondrial bioenergetics and stress resistance. Together, these findings demonstrate that context-specific, ANG-directed tDR biogenesis forms a crucial arm of the mitochondrial stress response.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104038"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage AMPK activated by oxidative stress drives profibrotic crosstalk with tubular cells to accelerate renal fibrosis after ischemic and reperfusion injury","authors":"Yuandong Tao ,&nbsp;Min Zhang ,&nbsp;Lei Chen ,&nbsp;Hongshuai Jia ,&nbsp;Yunjie Yang ,&nbsp;Yangyang Wu ,&nbsp;Pin Li ,&nbsp;Zhuyuan Wen ,&nbsp;Xiaowei Zhang ,&nbsp;Xiangmei Chen ,&nbsp;Xizhao Chen ,&nbsp;Xiubin Li ,&nbsp;Huixia Zhou","doi":"10.1016/j.redox.2025.104002","DOIUrl":"10.1016/j.redox.2025.104002","url":null,"abstract":"<div><div>Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that significantly increases the risk of progression to chronic kidney disease (CKD). Although oxidative stress has been implicated in this transition, the precise mechanisms through which it orchestrates inflammation and fibrosis during IRI-induced AKI-CKD progression remain poorly understood. In this study, we observed sustained reactive oxygen species (ROS) production in post-IRI kidneys. ROS were found to activate AMP-activated protein kinase (AMPK) in macrophages in a calcium-dependent manner. Conditional knockout of AMPKα1 in macrophages (<em>Lyz2</em>-Cre; <em>Prkaa1</em>-fl/fl mice) significantly attenuated renal fibrosis following IRI. Single-cell RNA sequencing analysis further revealed that AMPKα1 deletion reduced the accumulation of Arg1⁺ MMP12⁺ macrophages and diminished a profibrotic tubular epithelial cell (TEC) subpopulation marked by persistent expression of PDGFB and VCAM1. These macrophages were shown to interact with PDGFB⁺ VCAM1⁺ TECs. Mechanistically, macrophage-derived TWEAK signaling through its receptor Fn14 promoted PDGFB production in TECs, driving maladaptive changes and a fibrogenic phenotype. Importantly, TWEAK neutralization effectively mitigated the AKI-to-CKD transition. Together, our results identify macrophage AMPK as a key redox sensor that, upon activation by oxidative stress, initiates maladaptive macrophage-TEC crosstalk, ultimately promoting renal fibrosis and CKD progression.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"90 ","pages":"Article 104002"},"PeriodicalIF":11.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145894324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}