Apoptosis最新文献

{"title":"AIM2-PANoptosome-driven PANoptosis in hepatic lipid dysregulation induced by β-HCH and nanoplastics co-exposure","authors":"Qizhuan Lin,&nbsp;Helei Cai,&nbsp;Fan Yu,&nbsp;Changyong Gong,&nbsp;Yize Wu,&nbsp;Qiufang Wu,&nbsp;Feiqin Xie,&nbsp;Wenhui Xu,&nbsp;Shihua Chen,&nbsp;Xinxin Yao,&nbsp;Libo Jin,&nbsp;Renyi Peng","doi":"10.1007/s10495-025-02147-4","DOIUrl":"10.1007/s10495-025-02147-4","url":null,"abstract":"<div><p>Environmental pollutants pose an increasing threat to human health and ecosystems, with persistent organic pollutants (POPs) and nanoplastics (NPs) drawing significant attention due to their resistance to degradation, high mobility, and bioaccumulation. β-Hexachlorocyclohexane (β-HCH), a typical POP, poses a serious threat to organisms due to its long-term environmental persistence, despite being banned. In this study, we investigated the molecular mechanisms underlying hepatic lipid metabolism disorders induced by combined exposure to β-HCH and NPs using a zebrafish model and Hep G2 cell experiments. Histological staining, RT-qPCR, Western blotting, and immunofluorescence staining demonstrated that β-HCH and NPs co-exposure triggered multiple forms of programmed cell death (PCD), including apoptosis, pyroptosis, and necroptosis, through activation of the pyroptosis, apoptosis and necroptosis (PANoptosis) pathway mediated by the Absent in Melanoma 2 (AIM2)-PANoptosome complex, ultimately leading to lipid metabolism disturbances. RNA interference and gene overexpression experiments further revealed that down or overexpression of AIM2 significantly impacted PANoptosis, confirming the central regulatory role of AIM2 in this process. This study firstly elucidates the regulatory role of the AIM2-PANoptosome complex in the PANoptosis pathway under β-HCH and NPs co-exposure conditions. It provides valuable insights for developing intervention strategies targeting AIM2 for lipid metabolic diseases.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2340 - 2357"},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise","authors":"Nasreen Sulthana,&nbsp;Piyush Mittal,&nbsp;Ahsas Goyal,&nbsp;Suhas Ballal,&nbsp;Laxmidhar Maharana,&nbsp;Amita Joshi Rana,&nbsp;Yumna Khan,&nbsp;Kavita Goyal,&nbsp;Rakhi Mishra,&nbsp;Haider Ali,&nbsp;Gaurav Gupta,&nbsp;Md Sadique Hussain","doi":"10.1007/s10495-025-02148-3","DOIUrl":"10.1007/s10495-025-02148-3","url":null,"abstract":"<div><p>Apoptosis signal-regulating kinase 1 (ASK1), a redox-sensitive member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is a master regulator of neuronal apoptosis as well as neuroinflammation in neurodegenerative disorders (NDs). Under oxidative and endoplasmic reticulum stress conditions, ASK1 sets off a series of pathways, ultimately leading to impairment of cellular functions and the cell’s demise. The comprehensive review focuses on the diverse contributions of ASK1 to neurodegeneration driven by Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Human and animal evidence links dysregulated ASK1 signaling is related to amyloid deposition, tau hyperphosphorylation, neuroinflammation, abnormal protein folding, and subsequent neurodegeneration. ASK1 plays a role in tau hyperphosphorylation and amyloid-beta-induced neurotoxicity in AD. ASK1-mediated apoptosis of dopaminergic neurons caused by oxidative stress and aggregation of α-synuclein contributes to PD. Furthermore, ASK1 activation is associated with motor neuron degeneration in ALS related to endoplasmic reticulum stress caused by mutant SOD1. Moreover, the pathogenesis of HD involves the activation of ASK1 by the cellular stress caused by mutant huntingtin protein. ASK1 signaling potentiates inflammatory signals in MS because it is involved in demyelination and neuronal injury. Nonetheless, obstacles persist such as developing brain-targeted therapies, reducing adverse systemic effects, and defining disease-stage-specific functions of ASK1. This review aims to comprehensively examine the role of ASK1 signaling in major NDs, discuss its upstream and downstream regulatory mechanisms, and evaluate the current and emerging therapeutic strategies targeting ASK1.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2019 - 2041"},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting pyroptosis in myocardial inflammation and fibrosis: molecular mechanisms and therapeutic strategies","authors":"Yixiang Hu,&nbsp;Ying Huang,&nbsp;Jincai Guo,&nbsp;Xiang Liu,&nbsp;Ya Liu","doi":"10.1007/s10495-025-02151-8","DOIUrl":"10.1007/s10495-025-02151-8","url":null,"abstract":"<div><p>Pyroptosis is an inflammatory form of programmed cell death (PCD), driven by the activation of inflammasomes and inflammatory caspases. These molecular events trigger the proteolytic cleavage of gasdermin proteins, leading to membrane pores formation, cell lysis, and the subsequent release of cellular contents. Induction of pyroptosis amplifies inflammation, contributing to severe inflammatory responses and accelerating the pathogenesis of various chronic inflammation-related diseases. Myocardial fibrosis (MF) is characterized by the deposition of scar tissue in the heart, stemming from an aberrant wound healing response to inflammatory damage. It is a prevalent pathological feature in a range of cardiovascular diseases. Given the complex nature of wound repair and fibrosis following myocardial injury, treatments that target only specific contributors to disease pathogenesis show limited efficacy in mitigating fibrosis. While significant progress has been made in understanding the mechanisms underlying pyroptosis, its regulatory processes in MF remain incompletely understood, and strategies to improve clinical outcomes are still lacking. This review provides an in-depth examination of the latest insights into the regulatory mechanisms of pyroptosis, newly identified influencing factors, and its role in myocardial inflammation and fibrosis. Additionally, we discuss potential anti-fibrotic therapies targeting pyroptosis for the management of MF, highlighting challenges and future directions in this field.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"1989 - 2007"},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kim-1-targeted multimodal nanoprobes for early diagnosis and monitoring of sepsis-induced acute kidney injury","authors":"Qingjie Chen,&nbsp;Jianbo Yang,&nbsp;Mei Yang,&nbsp;Zhaoxia Luo,&nbsp;Yangyang Lei,&nbsp;Qing Zhang","doi":"10.1007/s10495-025-02141-w","DOIUrl":"10.1007/s10495-025-02141-w","url":null,"abstract":"<p>\u0000 Sepsis-induced acute kidney injury (AKI) is a critical condition characterized by high mortality and limited early diagnostic tools. This study presents the development of a novel multimodal nanoprobe, ⁶⁸Ga/99mTc@LTH-SPIONs, for targeted detection and monitoring of sepsis-induced AKI. By combining PET/SPECT imaging capabilities of radiolabeled isotopes (⁶⁸Ga and 99mTc) with the anatomical resolution of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI, the nanoprobe facilitates precise and non-invasive imaging. Surface modification with the LTH peptide, which specifically targets Kidney Injury Molecule-1 (Kim-1), enhances the nanoprobe’s diagnostic specificity. Extensive in vitro and in vivo evaluations revealed low cytotoxicity, excellent biocompatibility, and effective renal targeting, with metabolites predominantly cleared through urine. In a sepsis AKI mouse model, the nanoprobe provided sensitive and specific imaging, enabling early detection of kidney injury. This study underscores the potential of Kim-1-targeted nanoprobes as a powerful tool for elucidating cellular injury mechanisms and monitoring therapeutic interventions in AKI.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2316 - 2339"},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy","authors":"Sonia Iranpour,&nbsp;Maryam Arif,&nbsp;Eva Szegezdi","doi":"10.1007/s10495-025-02133-w","DOIUrl":"10.1007/s10495-025-02133-w","url":null,"abstract":"<div><p>Pore-forming proteins (PFPs), characterized by their ability to form pores or disrupt membranes are now recognized as key executioners of cell death, either as effectors of the immune system (non-cell-autonomous function), or of regulated cell death programs (cell autonomous function). To perforate membranes, most PFPs transition from water-soluble monomers or oligomers into multimeric and often supramolecular complexes, a process achieved via substantial structural transition of the PFP. Although they share the general ability to perforate cellular or intracellular membranes, PFPs differ in their membrane-binding preferences, the structural and functional characteristics of the pores they form (such as pore size, pore structure and ability to trigger membrane rupture) and the cell death mechanism they induce or execute. Herein, we review the specific traits of all key human PFPs, including their membrane specificity, regulation of their activity and the structure of the membrane pores they form, followed by insights into the therapeutic potential of PFPs and harnessing their abilities for cancer therapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"1961 - 1988"},"PeriodicalIF":8.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02133-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microplastics promote chemoresistance by mediating lipid metabolism and suppressing pyroptosis in colorectal cancer","authors":"Dongzhi Hu,&nbsp;Hui Liu,&nbsp;Yaoyang Guo,&nbsp;Haiyang Zhang,&nbsp;Minghan Qiu,&nbsp;Zhen Yang,&nbsp;Jie Hao,&nbsp;Zhansheng Jiang,&nbsp;Ming Gao,&nbsp;Xipeng Zhang,&nbsp;Mingqing Zhang","doi":"10.1007/s10495-025-02143-8","DOIUrl":"10.1007/s10495-025-02143-8","url":null,"abstract":"<div><p>Microplastics are ubiquitous environmental contaminants worldwide. Although studies have shown their potential to harm human health, the relationship between microplastics and tumors remains unclear. The intestine is the primary site for microplastics absorption, thus the impact of microplastics on colorectal cancer merits further investigation. Our results indicate that the endocytosis protein clathrin, highly expressed in cancer cells, plays a crucial role in the massive ingestion of microplastics. Further research reveals that microplastics ingestion enhances lipid absorption in colorectal cancer cells by activating the NF-κB signaling pathway. Accumulation of lipids, in turn, suppresses pyroptosis by inhibiting NLRP3/Caspase-1/GSDMD axis, thereby promoting cellular drug resistance. Moreover, microplastics accelerate colorectal cancer development in mice and enhance tumor resistance to oxaliplatin. In summary, microplastics regulate lipid metabolism and pyroptosis in colorectal cancer, emerging as a novel contributor to chemotherapy resistance in colorectal cancer against the backdrop of escalating microplastics pollution.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2287 - 2300"},"PeriodicalIF":8.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin alleviates sodium sulfite-induced osteoporosis in mice via suppression of the ferroptosis pathway","authors":"Qiuping He,&nbsp;Lei Xie,&nbsp;Haining Peng,&nbsp;Xiao Xiao,&nbsp;Tengbo Yu","doi":"10.1007/s10495-025-02135-8","DOIUrl":"10.1007/s10495-025-02135-8","url":null,"abstract":"<div><p>Sodium sulfite (SS) is a common food additive that is widely absorbed and distributed throughout the body, but its excessive intake has been linked to adverse health effects. Here, we investigate the impact of chronic SS exposure on bone tissue and the underlying mechanisms. Using a mouse model, we demonstrate that prolonged SS exposure induces significant bone loss, which correlates with alterations in ferroptosis-related markers. In vitro, SS exposure activates ferroptosis, which is characterized by elevated reactive oxygen species levels and impaired osteogenic differentiation in MC3T3 cells. Notably, melatonin, a potent endogenous antioxidant, mitigates SS-induced oxidative stress, inhibits ferroptosis, restores osteoblast function, and alleviates bone loss in mice. These findings highlight ferroptosis as a critical contributor to SS-induced osteoporosis and identify melatonin as a promising therapeutic agent for its prevention and treatment.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2301 - 2315"},"PeriodicalIF":8.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02135-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting autophagy and related pathways: pioneering new horizons in cataract therapy","authors":"Mehrdad Hashemi,&nbsp;Pezhman Shafiei Asheghabadi,&nbsp;Mahdi Moassesfar,&nbsp;Roya Malek Mohammadi,&nbsp;Nazanin Rafedoust,&nbsp;Maedeh Razeh,&nbsp;Yeganeh Esfahaniolasl,&nbsp;Mahsa Mirzayi,&nbsp;Sahar Keikhavani,&nbsp;Katrin Tajbakhsh,&nbsp;Hajar Heidari,&nbsp;Russel J. Reiter,&nbsp;Mina Alimohammadi,&nbsp;Afshin Taheriazam,&nbsp;Najma Farahani,&nbsp;Kiavash Hushmandi,&nbsp;Maliheh Entezari","doi":"10.1007/s10495-025-02134-9","DOIUrl":"10.1007/s10495-025-02134-9","url":null,"abstract":"<div><p>Autophagy is a critical catabolic pathway that facilitates the degradation of intracellular components through lysosomal activity, originally recognized for its role in nutrient recycling during starvation. Recent research has expanded our understanding of autophagy, revealing its involvement in various physiological processes essential for cellular, tissue, and organismal homeostasis. Dysregulation of autophagy has been linked to numerous diseases, including ocular conditions such as cataracts. In human lens fibers, autophagic vesicles containing mitochondria or mitochondrial fragments have been identified, underscoring the importance of autophagy in maintaining lens integrity and transparency. Disruptions in organelle elimination can lead to increased reactive oxygen species (ROS), altering lens homeostasis and contributing to cataract formation. Recent studies have highlighted the complex interplay between autophagy and lens epithelial cells (LECs) in both age-related and diabetic cataract development. In age-related cataracts, increased autophagic activity coincides with elevated apoptosis in LECs, suggesting a bidirectional regulatory role of autophagy in cellular senescence. Additionally, the degradation of SQSTM1/p62 during oxidative stress implicates autophagy in the apoptotic processes associated with senile cataracts. In diabetic cataracts, high glucose levels disrupt the relationship between autophagy and epithelial-mesenchymal transition (EMT) in LECs via the Notch signaling pathway, leading to impaired autophagic function and subsequent cataractogenesis. These findings indicate that autophagy dysregulation is a significant contributor to the pathophysiology of various cataract types. Future research should focus on exploring the therapeutic potential of modulating autophagy to prevent or treat cataracts, investigating specific signaling pathways involved, and identifying biomarkers for early detection. By elucidating the molecular mechanisms underlying autophagy’s role in cataract formation, novel targeted therapies may emerge, providing hope for improved management and prevention of this prevalent ocular pathology.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"1931 - 1960"},"PeriodicalIF":8.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin-Inspired 6-O-Carboxymethyl-N-Acetylglucosamine: A potent antitumor agent with enhanced efficacy","authors":"Ziwen Qiao,&nbsp;Guangmin Zhang,&nbsp;Xin Chen,&nbsp;Yuefa Zhang,&nbsp;Sudan Zhang,&nbsp;Xiuheng Qin,&nbsp;Ammara Sohail,&nbsp;Xiaohui Xu,&nbsp;Jiane Liu,&nbsp;Baoqin Han,&nbsp;Daijie Wang,&nbsp;Xiangyan Zhang,&nbsp;Zheng Wang","doi":"10.1007/s10495-025-02139-4","DOIUrl":"10.1007/s10495-025-02139-4","url":null,"abstract":"<div><p>Aspirin, widely recognized for its anti-inflammatory and cardioprotective effects, has also shown potential as a cancer therapeutic. However, its clinical application is hindered by severe adverse effects. Here, we explore 6-<i>O</i>-Carboxymethyl-<i>N</i>-Acetylglucosamine (CM-NAG) a novel derivative of <i>N</i>-acetylglucosamine, designed to mimic the structural and functional properties of aspirin. CM-NAG significantly inhibits the viability of both colorectal and pancreatic cancer cells. In colorectal cancer cells, CM-NAG also suppressed migration and invasion and induced apoptosis more effectively than aspirin. Mechanistically, CM-NAG upregulated phosphoenolpyruvate carboxykinase 2 (PCK2), a key regulator of gluconeogenesis in colorectal cancer cells. In a xenograft model, CM-NAG reduced tumor size and improved histopathological outcomes, while showing no significant toxicity in major organs. The expression of PCK2 in CRC tissues was significantly lower than in cancer-adjacent tissues, according immunohistochemistry analysis. Clinical analysis revealed high PCK2 expression in colorectal cancer tissues correlates with better disease-free survival, supporting PCK2 as a promising therapeutic target. These findings suggest that CM-NAG may represent a next-generation antitumor agent with enhanced efficacy and safety compared to aspirin, offering new prospects for cancer treatment.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2254 - 2268"},"PeriodicalIF":8.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSLP mitigates post-infarction myocardial remodeling by promoting eosinophil recruitment and inhibiting JAK1–STAT5-mediated ferroptosis","authors":"Yunzhe Wang,&nbsp;Chenxi Cao,&nbsp;Tinglan Fu,&nbsp;Fengyi Yu,&nbsp;Jinyue Qi,&nbsp;Gangqiong Liu,&nbsp;Jinying Zhang","doi":"10.1007/s10495-025-02137-6","DOIUrl":"10.1007/s10495-025-02137-6","url":null,"abstract":"<div><p>Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality globally, often leading to heart failure due to excessive inflammation and fibrosis. Thymic stromal lymphopoietin (TSLP), a cytokine primarily involved in immune regulation, has recently been identified as a key player in cardiovascular health. However, its role in modulating inflammation and fibrosis after AMI is not fully understood. This study investigates how TSLP mediates anti-inflammatory effects and reduces fibrosis, ultimately improving heart function in a mouse model of AMI. We established a TSLP knockout mouse strain and performed left anterior descending (LAD) coronary artery ligation to create an AMI model. This was used to investigate the role of TSLP in eosinophil (EOS) recruitment and fibrosis alleviation. Additionally, EOS depletion, JAK-STAT pathway inhibition, and ferroptosis were employed to analyze potential mediating factors. The extent of cardiac tissue fibrosis was evaluated using histological staining. Inflammatory cytokine levels and EOS were assessed through ELISA and flow cytometry. Western blotting was conducted to detect proteins related to ferroptosis and the JAK-STAT pathway. TSLP deficiency significantly exacerbated myocardial remodeling in AMI mice, while TSLP treatment markedly reduced cardiac fibrosis following AMI, with a notable decrease in collagen deposition within the heart tissue. In Transwell assays, TSLP effectively recruited EOSs, and in vivo experiments demonstrated that TSLP promoted the resolution of acute-phase inflammation (within one week), a process that could be blocked by EOS depletion. TSLP promotes the resolution of post-infarction inflammation and inhibits fibrosis by recruiting EOSs to the heart. This highlights the potential of targeting the TSLP-EOS axis as a therapeutic strategy to improve cardiac function and reduce post-AMI complications.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><img></picture></div></div></figure></div><p>This schematic illustrates the role of TSLP in regulating eosinophil (EOS) recruitment and protecting cardiomyocytes following acute myocardial infarction (AMI). Under pathological conditions, reduced TSLP expression leads to overactivation of the JAK1–STAT5 pathway, repression of <i>SLC7A11</i> transcription, increased ferroptosis, and mitochondrial damage, accompanied by impaired EOS recruitment and excessive fibrosis. In contrast, TSLP supplementation inhibits the JAK1 pathway, promotes EOS recruitment, downregulates pro-inflammatory cytokine expression, restores mitochondrial structural integrity, and suppresses ferroptosis by upregulating SLC7A11 and glutathione (GSH) synthesis, thereby facilitating optimal fibrotic repair.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2269 - 2286"},"PeriodicalIF":8.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-025-02137-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}