Cell Proliferation最新文献

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Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency. 负责核仁重塑的rDNA的超转录是获得多能性的关键。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-05-04 DOI: 10.1111/cpr.70052
Yuchen Sun, Xinglin Hu, Xingwei Huang, Wenyao Zhou, Shubing Lan, Hui Zhang, Guangming Wu, Lei Lei
{"title":"Hypertranscription of rDNA Responsible for Nucleolar Remodelling is a Doorman for Acquiring Pluripotency.","authors":"Yuchen Sun, Xinglin Hu, Xingwei Huang, Wenyao Zhou, Shubing Lan, Hui Zhang, Guangming Wu, Lei Lei","doi":"10.1111/cpr.70052","DOIUrl":"https://doi.org/10.1111/cpr.70052","url":null,"abstract":"<p><p>Ribosome biogenesis occurs within the nucleolus, with the initial step being the transcription of ribosomal DNA (rDNA). Although rDNA transcription is limited in somatic cells, it is more active in stem cells. Nevertheless, the mechanisms involved in somatic cell reprogramming remain elusive. Both somatic and stem cell nucleoli exhibit a reticular structure. However, under the electron microscope, we identified an intermediate nucleolar state during reprogramming. This state underwent changes characterised by rDNA hypertranscription, resulting in an enlarged nucleolus, enhanced activity of nucleolus organiser regions (NORs), and a transition from the reticular nucleolar type to an intermediate state of reprogramming, whose three liquid phase boundaries are blurred. Our research revealed that Oct4 was directly targeted to the rDNA enhancer region, promoting its hypertranscription and nucleolar enlargement during reprogramming. Using rDNA transcriptional inhibitors, we proved that nucleolar remodelling and subsequent reprogramming are halted by inhibiting rDNA transcription. But why could rDNA transcriptional activity influence reprogramming? Our findings elucidate that the active nucleoli have the capability to release perinucleolar heterochromatin. By joint analysis of Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and RNA-seq, we have characterised the perinucleolar chromatin released by the nucleolus in a reprogramming intermediate state. The released chromatin mainly impacted mesenchymal-to-epithelial transition (MET)-related genes. MET is a stage of silencing of mesenchymal genes, accompanied by the activation of epithelial genes. Concurrently, the morphology of mouse embryonic fibroblast cells (MEFs) transitions from elongated spindle-shaped cells to short roundish forms, exhibiting a propensity to cluster together. MET was considered an early event in reprogramming; our findings suggested that nucleolar remodelling occurred before MET.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70052"},"PeriodicalIF":5.9,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974445","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}
引用次数: 0
THER: Integrative Web Tool for Tumour Hypoxia Exploration and Research. THER:肿瘤缺氧探索和研究的综合网络工具。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-05-01 DOI: 10.1111/cpr.70053
Yasi Zhang, Huiying Liu, Pengpeng Zhang, BiCheng Ye, Haoxuan Ying, Hong Yang, Jian Zhang, Nan Zhang, Kailai Li, Ting Wei, Aimin Jiang, Anqi Lin, Peng Luo
{"title":"THER: Integrative Web Tool for Tumour Hypoxia Exploration and Research.","authors":"Yasi Zhang, Huiying Liu, Pengpeng Zhang, BiCheng Ye, Haoxuan Ying, Hong Yang, Jian Zhang, Nan Zhang, Kailai Li, Ting Wei, Aimin Jiang, Anqi Lin, Peng Luo","doi":"10.1111/cpr.70053","DOIUrl":"https://doi.org/10.1111/cpr.70053","url":null,"abstract":"","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70053"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987285","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}
引用次数: 0
Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer. 泛素-蛋白酶体系统在非小细胞肺癌中的作用机制及治疗潜力。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-05-01 DOI: 10.1111/cpr.70050
Guangyao Zhou, Jiaxiong Tan, Pengpeng Zhang, Zhaokai Zhou, Lianmin Zhang, Zhenfa Zhang
{"title":"Mechanistic Insights and Therapeutic Potentials of Ubiquitin-Proteasome System in Non-Small Cell Lung Cancer.","authors":"Guangyao Zhou, Jiaxiong Tan, Pengpeng Zhang, Zhaokai Zhou, Lianmin Zhang, Zhenfa Zhang","doi":"10.1111/cpr.70050","DOIUrl":"https://doi.org/10.1111/cpr.70050","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Despite advancements in gene targeted therapies and immunotherapies, high heterogeneity contributes to limited efficacy and therapeutic resistance. Ubiquitination, a crucial post-translational modification that regulates protein stability and degradation, plays a significant role in cancer pathogenesis by influencing key oncogenic pathways and tumour progression. This review systematically explores the ubiquitin-proteasome system (UPS) and its potential as a therapeutic target for NSCLC. We highlight recent preclinical and clinical studies focusing on ubiquitination-related biomarkers, drug targets and emerging therapies like proteasome inhibitors and Proteolysis-targeting chimeras (PROTACs). By exploring the impact of the UPS on tumour biology, the progression of NSCLC and its response to therapy, we aim to underscore the potential of targeting the ubiquitination-deubiquitination system as a complementary or synergistic approach to existing therapeutic strategies in NSCLC, thereby enhancing patient outcomes and overcoming treatment resistance.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70050"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982192","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}
引用次数: 0
GANT61 Modulates Autophagy and Lipid Metabolism in Ovarian Cancer. GANT61调节卵巢癌自噬和脂质代谢。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-05-01 DOI: 10.1111/cpr.70051
Yibin Pan, Lingfeng Chen, Jinlu Shen, Shihao Hong, Xiaojing Guan, Xudong Ma, Rongrong Tang, Meifei Lu, Fangying Sun, Shanliang Shang, Yongdong Dai, Zhaokai Zhou, Songying Zhang, Jianhua Yang
{"title":"GANT61 Modulates Autophagy and Lipid Metabolism in Ovarian Cancer.","authors":"Yibin Pan, Lingfeng Chen, Jinlu Shen, Shihao Hong, Xiaojing Guan, Xudong Ma, Rongrong Tang, Meifei Lu, Fangying Sun, Shanliang Shang, Yongdong Dai, Zhaokai Zhou, Songying Zhang, Jianhua Yang","doi":"10.1111/cpr.70051","DOIUrl":"https://doi.org/10.1111/cpr.70051","url":null,"abstract":"<p><p>GANT61 induced autophagy via the AKT pathway and promoted the accumulation of lipid droplets in both cell lines. The molecular mechanism behind this lipid accumulation appears to involve the mediation of SREBP1. Furthermore, the combination of GANT61 with CQ/Fatostatin significantly inhibited the proliferation and clonogenicity of SKOV3 and SKOV3PTX cells.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70051"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962755","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}
引用次数: 0
Extrachromosomal Circular DNA in Cancer: Mechanisms and Clinical Applications. 染色体外环状DNA在癌症中的作用:机制和临床应用。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-29 DOI: 10.1111/cpr.70040
Jiajia Li, Peng Luo, Zhengrui Li, Qi Wang, Xufeng Huang, Keliang Wang, Ruo Wang, Runzhi Chen
{"title":"Extrachromosomal Circular DNA in Cancer: Mechanisms and Clinical Applications.","authors":"Jiajia Li, Peng Luo, Zhengrui Li, Qi Wang, Xufeng Huang, Keliang Wang, Ruo Wang, Runzhi Chen","doi":"10.1111/cpr.70040","DOIUrl":"https://doi.org/10.1111/cpr.70040","url":null,"abstract":"<p><p>Extrachromosomal circular DNA (eccDNA) has emerged as a critical area of cancer research due to its ubiquitous presence in tumour cells and significant role in tumorigenesis, progression and drug resistance. Recent studies demonstrate that eccDNA promotes cancer progression by influencing genomic instability, amplifying oncogenes, regulating gene expression and enhancing tumour cell adaptability to adverse conditions. While the precise mechanisms underlying eccDNA formation and its biological functions remain unclear, its potential applications in cancer diagnosis, prognosis and targeted therapy are gaining increasing recognition. This review summarises the latest advancements in eccDNA research, highlighting its potential as both a biomarker and a therapeutic target. Additionally, it emphasises the translational potential of eccDNA in clinical diagnostics and personalised treatment strategies, offering new perspectives for future cancer research and innovative therapies.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70040"},"PeriodicalIF":5.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954240","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}
引用次数: 0
Synergistical Induction of Apoptosis via Cold Atmospheric Plasma and Nanohydroxyapatite for Selective Inhibition of Oral Squamous Cell Carcinoma in Tumour Microenvironment. 低温大气等离子体和纳米羟基磷灰石协同诱导细胞凋亡选择性抑制口腔鳞状细胞癌肿瘤微环境。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-29 DOI: 10.1111/cpr.70041
Wenting Qi, Hanghang Liu, Huaze Liu, Yuxuan Guo, Li Wu, Chongyun Bao, Xian Liu
{"title":"Synergistical Induction of Apoptosis via Cold Atmospheric Plasma and Nanohydroxyapatite for Selective Inhibition of Oral Squamous Cell Carcinoma in Tumour Microenvironment.","authors":"Wenting Qi, Hanghang Liu, Huaze Liu, Yuxuan Guo, Li Wu, Chongyun Bao, Xian Liu","doi":"10.1111/cpr.70041","DOIUrl":"https://doi.org/10.1111/cpr.70041","url":null,"abstract":"<p><p>Surgical resection, radiotherapy and chemotherapy are the primary strategies of treating cancers globally. However, the current treatment methods bring new disease burdens to patients due to postoperative complications and multiple side effects, especially in surface tumours such as oral squamous cell carcinoma (OSCC). In this study, we developed a microwave cold atmospheric plasma (CAP) device in conjunction with tumour microenvironment-responsive nanohydroxyapatite (nHA) for the first time. The synergistic effects of CAP and nHA combined application on OSCC were evaluated in both in vitro and in vivo experiments. The synergistic effects of CAP and pH-responsive NH<sub>2</sub>-nHA on the apoptosis, intracellular reactive oxygen species (ROS) and calcium ion concentration of OSCC cells were investigated in vitro. The synergistic induction of CAP with NH<sub>2</sub>-nHA exhibited optimal tumour-specific inhibitory effects on OSCC. The results revealed that the combined application of CAP with NH<sub>2</sub>-nHA induced apoptosis of tumour cells in vitro and killed 84.0% of tumours in vivo. Mechanistically, CAP enhances extracellular ROS production, while NH<sub>2</sub>-nHA amplifies intracellular calcium ion (Ca<sup>2+</sup>) concentrations, synergistically increasing intracellular ROS levels to provoke oxidative stress in OSCC cells, ultimately triggering the mitochondrial apoptosis pathway. In conclusion, the combined utilisation of CAP and NH<sub>2</sub>-nHA presents a promising avenue as a novel, selective, and non-invasive strategy in the management of OSCC.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70041"},"PeriodicalIF":5.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981687","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}
引用次数: 0
Mechanical Force Regulates the Paracrine Function of ADSCs to Promote the Adipose-Regenerating Effects of AAM by Regulating Angiogenesis and the Inflammatory Response. 机械力调节ADSCs的旁分泌功能,通过调节血管生成和炎症反应促进AAM的脂肪再生作用
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-27 DOI: 10.1111/cpr.70045
Yining Wang, Luyu Zhang, Jiaxuan Liu, Yuchao Yang, Zhenyu Bi, Jun Ouyang
{"title":"Mechanical Force Regulates the Paracrine Function of ADSCs to Promote the Adipose-Regenerating Effects of AAM by Regulating Angiogenesis and the Inflammatory Response.","authors":"Yining Wang, Luyu Zhang, Jiaxuan Liu, Yuchao Yang, Zhenyu Bi, Jun Ouyang","doi":"10.1111/cpr.70045","DOIUrl":"https://doi.org/10.1111/cpr.70045","url":null,"abstract":"<p><p>Conditioned medium (CM), obtained by mechanical regulation of the paracrine activity of ADSCs, was fused with acellular adipose matrix (AAM) and methyl cellulose (MC) to synthesize a composite hydrogel which was grafted onto nude mice. The composite hydrogel could promote soft tissue regeneration by regulating the level of vascular regeneration and inflammation.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70045"},"PeriodicalIF":5.9,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978032","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}
引用次数: 0
Elucidating the Role and Mechanism of Alpha-Enolase in Senescent Amelioration via Metabolic Reprogramming. α -烯醇化酶通过代谢重编程改善衰老的作用和机制。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-27 DOI: 10.1111/cpr.70049
Yun Haeng Lee, Hyunwoong Lim, Gyungmin Kim, Geonhee Jang, Myeong Uk Kuk, Ji Ho Park, Jee Hee Yoon, Yoo Jin Lee, Duyeol Kim, Byeonghyeon So, Minseon Kim, Hyung Wook Kwon, Youngjoo Byun, Joon Tae Park
{"title":"Elucidating the Role and Mechanism of Alpha-Enolase in Senescent Amelioration via Metabolic Reprogramming.","authors":"Yun Haeng Lee, Hyunwoong Lim, Gyungmin Kim, Geonhee Jang, Myeong Uk Kuk, Ji Ho Park, Jee Hee Yoon, Yoo Jin Lee, Duyeol Kim, Byeonghyeon So, Minseon Kim, Hyung Wook Kwon, Youngjoo Byun, Joon Tae Park","doi":"10.1111/cpr.70049","DOIUrl":"https://doi.org/10.1111/cpr.70049","url":null,"abstract":"<p><p>Senescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis metabolism has not been fully elucidated. Here, we identified a candidate compound, an oxazole analogue (KB2764), that can improve senescence. To elucidate the mechanism of the KB2764, we investigated the interacting proteins. KB2764 interacted with alpha-enolase (ENO1) and pyruvate kinase M (PKM), ultimately allowing PKM to phosphorylate ENO1. KB2764 consequently increased mitochondrial ATP production and reduced reliance on glycolysis. Knockdown of the ENO1 experiment in senescent cells demonstrates that regulation of ENO1 activity is a prerequisite for recovery of mitochondrial function. Furthermore, the action of KB2764 extends its application to extend the lifespan of Caenorhabditis elegans. Taken together, our findings reveal a novel mechanism by which senescence is ameliorated through metabolic reprogramming and mitochondrial functional recovery via KB2764-mediated regulation of ENO1 protein activity.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70049"},"PeriodicalIF":5.9,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969509","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}
引用次数: 0
Intelligent Manufacturing for Osteoarthritis Organoids. 骨关节炎类器官的智能制造。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-26 DOI: 10.1111/cpr.70043
Xukun Lyu, Jian Wang, Jiacan Su
{"title":"Intelligent Manufacturing for Osteoarthritis Organoids.","authors":"Xukun Lyu, Jian Wang, Jiacan Su","doi":"10.1111/cpr.70043","DOIUrl":"https://doi.org/10.1111/cpr.70043","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, imposing a substantial global disease burden. However, its pathogenesis remains incompletely understood, and effective treatment strategies are still lacking. Organoid technology, in which stem cells or progenitor cells self-organise into miniature tissue structures under three-dimensional (3D) culture conditions, provides a promising in vitro platform for simulating the pathological microenvironment of OA. This approach can be employed to investigate disease mechanisms, carry out high-throughput drug screening and facilitate personalised therapies. This review summarises joint structure, OA pathogenesis and pathological manifestations, thereby establishing the disease context for the application of organoid technology. It then examines the components of the arthrosis organoid system, specifically addressing cartilage, subchondral bone, synovium, skeletal muscle and ligament organoids. Furthermore, it details various strategies for constructing OA organoids, including considerations of cell selection, pathological classification and fabrication techniques. Notably, this review introduces the concept of intelligent manufacturing of OA organoids by incorporating emerging engineering technologies such as artificial intelligence (AI) into the organoid fabrication process, thereby forming an innovative software and hardware cluster. Lastly, this review discusses the challenges currently facing intelligent OA organoid manufacturing and highlights future directions for this rapidly evolving field. By offering a comprehensive overview of state-of-the-art methodologies and challenges, this review anticipates that intelligent, automated fabrication of OA organoids will expedite fundamental research, drug discovery and personalised translational applications in the orthopaedic field.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70043"},"PeriodicalIF":5.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974446","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}
引用次数: 0
KYNA Ameliorates Hepatic Ischemia-Reperfusion Injury by Activating the Hippo Signalling Pathway via FTO-Dependent m6A Demethylation of LATS1. KYNA通过fto依赖的LATS1 m6A去甲基化激活Hippo信号通路,改善肝缺血再灌注损伤。
IF 5.9 1区 生物学
Cell Proliferation Pub Date : 2025-04-25 DOI: 10.1111/cpr.70048
Wenjie Zheng, Xiaowen Wang, Haoqi Chen, Kaiming He, Xijing Yan, Yuan Zhang, Yang Yang, Peng Zhang, Wenfeng Zhu, Shuguang Zhu, Hua Li
{"title":"KYNA Ameliorates Hepatic Ischemia-Reperfusion Injury by Activating the Hippo Signalling Pathway via FTO-Dependent m6A Demethylation of LATS1.","authors":"Wenjie Zheng, Xiaowen Wang, Haoqi Chen, Kaiming He, Xijing Yan, Yuan Zhang, Yang Yang, Peng Zhang, Wenfeng Zhu, Shuguang Zhu, Hua Li","doi":"10.1111/cpr.70048","DOIUrl":"https://doi.org/10.1111/cpr.70048","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion injury (HIRI) substantially influences the prognosis of liver transplant recipients. Although kynurenic acid (KYNA) has been associated with protective effects against ischemia-reperfusion injury in various organs, the precise mechanisms underlying its protective role in HIRI are not well elucidated. In this study, a 70% mouse HIRI model and an in vitro hypoxia/reoxygenation model were employed to examine the protective effects of KYNA on HIRI. In this study, we illustrate that KYNA influences the methylation status of the Hippo signalling pathway by enhancing the expression of the fat mass and obesity-associated gene (FTO). Within this pathway, large tumour suppressor kinase 1 (LATS1) is identified as a direct target of FTO. Moreover, the stability of LATS1 mRNA exhibits an inverse correlation with FTO levels and is modulated through its interaction with YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2). The reduction in LATS1 expression facilitated Yes-associated protein (YAP) nuclear translocation, decreased hepatocyte apoptosis, and mitigated HIRI. Clinically, elevated levels of serum KYNA correlate with a diminished severity of liver injury post-transplantation. our work revealed that KYNA possesses significant clinical translational potential for the prevention of HIRI, and further exploration of its underlying mechanisms was conducted.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70048"},"PeriodicalIF":5.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967221","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}
引用次数: 0
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