Acta biochimica et biophysica Sinica最新文献

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The combination of fatigue with the serum GCSF improves the performance of serological screening for frailty. 疲劳与血清GCSF的结合提高了虚弱的血清学筛查的性能。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-26 DOI: 10.3724/abbs.2025007
Jiaming Yu, Jie Chen, Xueying Ji, Yixuan Qiu, Yan Zhang, Jiaofeng Wang, Xiangqi Li, Chaobao Zhang, Zhijun Bao
{"title":"The combination of fatigue with the serum GCSF improves the performance of serological screening for frailty.","authors":"Jiaming Yu, Jie Chen, Xueying Ji, Yixuan Qiu, Yan Zhang, Jiaofeng Wang, Xiangqi Li, Chaobao Zhang, Zhijun Bao","doi":"10.3724/abbs.2025007","DOIUrl":"https://doi.org/10.3724/abbs.2025007","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497489","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}
引用次数: 0
Corrigendum to: Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition. 下调整合素亚单位α 7 (ITGA7)可通过调节上皮细胞向间质细胞的转变促进甲状腺乳头状癌细胞的增殖、侵袭和迁移。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-25 DOI: 10.3724/abbs.2024200
Yaoyao Guan, Adheesh Bhandari, Erjie Xia, Lingguo Kong, Xiaohua Zhang, Ouchen Wang
{"title":"Corrigendum to: Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition.","authors":"Yaoyao Guan, Adheesh Bhandari, Erjie Xia, Lingguo Kong, Xiaohua Zhang, Ouchen Wang","doi":"10.3724/abbs.2024200","DOIUrl":"10.3724/abbs.2024200","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"325"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765442","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}
引用次数: 0
p53-dependent chromatin relaxation is required for DNA double-strand break repair. p53依赖性染色质松弛是DNA双链断裂修复所必需的。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-25 DOI: 10.3724/abbs.2025008
Hongyu Chen, Jin Shan, Wenjing Qi, Lili Chen, Xianlu Zeng
{"title":"p53-dependent chromatin relaxation is required for DNA double-strand break repair.","authors":"Hongyu Chen, Jin Shan, Wenjing Qi, Lili Chen, Xianlu Zeng","doi":"10.3724/abbs.2025008","DOIUrl":"10.3724/abbs.2025008","url":null,"abstract":"<p><p>The tumor suppressor p53, an indispensable nuclear transcription factor, plays a central role in orchestrating cellular responses when DNA damage occurs. In this study, we demonstrate that in the initial phases of DNA double-strand break (DSB) repair, p53 is rapidly recruited to sites of damage and the surrounding chromatin, where it enhances DSB repair efficiency. This enhancement occurs through the modulation of chromatin dynamics and the promotion of a more relaxed chromatin configuration, a process influenced by p53 in response to DSB-inducing factors such as etoposide, ultraviolet radiation, and nucleases. These results underscore the pivotal function of p53 as a rapid responder to DSBs, delineating a significant departure from its traditionally recognized role as a downstream transcriptional regulator in DNA damage repair processes. This study emphasizes that the direct engagement of p53 in DNA repair through chromatin structure regulation extends beyond its established involvement in UV irradiation-induced nucleotide excision repair (NER), demonstrating analogous mechanistic attributes in the context of DSB repair. This newly illuminated perspective enhances our understanding of the multifaceted roles of p53 in genome stability and integrity.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"701-711"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497492","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}
引用次数: 0
Corrigendum to: HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells. hspa8介导的CLPP蛋白的稳定性调节顺铂耐药卵巢癌细胞的线粒体自噬。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-25 DOI: 10.3724/abbs.2024243
Xinxin Kou, Xiaoxia Yang, Zheng Zhao, Lei Li
{"title":"Corrigendum to: HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells.","authors":"Xinxin Kou, Xiaoxia Yang, Zheng Zhao, Lei Li","doi":"10.3724/abbs.2024243","DOIUrl":"10.3724/abbs.2024243","url":null,"abstract":"","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"326"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885193","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}
引用次数: 0
KAT8 facilitates the proliferation of cancer cells through enhancing E7 function in HPV-associated cervical cancer. KAT8通过增强E7在hpv相关宫颈癌中的功能促进癌细胞的增殖。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-24 DOI: 10.3724/abbs.2025022
Anli Xu, Xiaoming Yang, Junwei Zhao, Shujun Kong, Qing Tang, Xiangzhi Li, Hongmei Qu, Guoyun Wang
{"title":"KAT8 facilitates the proliferation of cancer cells through enhancing E7 function in HPV-associated cervical cancer.","authors":"Anli Xu, Xiaoming Yang, Junwei Zhao, Shujun Kong, Qing Tang, Xiangzhi Li, Hongmei Qu, Guoyun Wang","doi":"10.3724/abbs.2025022","DOIUrl":"https://doi.org/10.3724/abbs.2025022","url":null,"abstract":"<p><p>Persistent human papillomavirus (HPV) infection serves as the principal etiological factor in cervical cancer, with the oncoprotein E7, which is encoded by the virus, playing a key role in tumorigenesis. However, targeted therapeutic strategies against E7 remain underexplored. KAT8, a lysine acetyltransferase, significantly contributes to oncogenesis through the regulation of transcription. However, its involvement in cervical cancer remains inadequately characterized. This study employs HPV18-positive HeLa and HPV16-positive SiHa cell lines to investigate how KAT8 modulates E7 expression and function in cervical cancer cells. Upon <i>KAT8</i> knockdown, a marked reduction in cell viability is observed, alongside a decrease in E7 expression. This is associated with elevated level of retinoblastoma protein (pRb) and decreased E2F1 expression, indicating that KAT8 depletion inhibits E7 expression, resulting in E2F1 inactivation and cell cycle arrest. Furthermore, KAT8 directly binds to the promoter regions of the HPV18 LCR, enhancing the transcription of the HPV18 E7 gene. This study also demonstrates that KAT8 is essential for the acetylation of E7 and plays a critical role in facilitating the interaction between pRb/E2F1 and E7 in cervical cancer cells. In conclusion, these results highlight KAT8 as a key driver of cervical cancer progression, promoting the expression of HPV E7 and its associated oncogenic signaling pathways.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482001","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}
引用次数: 0
Divergent roles of PKM2 in regulating PD-L1 and PD-L2 expression and their implications in human and mouse cancer models. PKM2在调节PD-L1和PD-L2表达中的不同作用及其在人和小鼠癌症模型中的意义
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-21 DOI: 10.3724/abbs.2025019
Shuo He, Shujuan Luo, Bangwu Cai, Jiao Chen, Yao Zhang, Feng Zhao, Qing Liu, Tao Liu, Wei Wang, Tianyuan Peng, Xiaomei Lu, Shutao Zheng
{"title":"Divergent roles of PKM2 in regulating PD-L1 and PD-L2 expression and their implications in human and mouse cancer models.","authors":"Shuo He, Shujuan Luo, Bangwu Cai, Jiao Chen, Yao Zhang, Feng Zhao, Qing Liu, Tao Liu, Wei Wang, Tianyuan Peng, Xiaomei Lu, Shutao Zheng","doi":"10.3724/abbs.2025019","DOIUrl":"https://doi.org/10.3724/abbs.2025019","url":null,"abstract":"<p><p>Cancer cells evade immune detection through checkpoint molecules like PD-L1 and PD-L2 which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of pyruvate kinase M2 (PKM2) in modulating the immune checkpoint molecules PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. <i>PKM2</i> knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of <i>PD-L1</i> and <i>PD-L2</i>. <i>In silico</i> analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8 <sup>+</sup> T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of <i>PKM2</i> results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466627","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}
引用次数: 0
Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoE -/- mice. 丙酮酸脱氢酶减轻hcy诱导的ApoE -/-小鼠巨噬细胞自噬。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-21 DOI: 10.3724/abbs.2025021
Qiujun Liu, Feng Li, Shutong Hu, Ning Ding, Fang Ma, Yinju Hao, Guizhong Li, Jiantuan Xiong, Huiping Zhang, Yideng Jiang
{"title":"Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoE <sup>-/-</sup> mice.","authors":"Qiujun Liu, Feng Li, Shutong Hu, Ning Ding, Fang Ma, Yinju Hao, Guizhong Li, Jiantuan Xiong, Huiping Zhang, Yideng Jiang","doi":"10.3724/abbs.2025021","DOIUrl":"https://doi.org/10.3724/abbs.2025021","url":null,"abstract":"<p><p>Macrophages play a protective role in atherosclerosis, whereas homocysteine (Hcy) is recognized as an independent risk factor for atherosclerosis. Defects in macrophage autophagy contribute to the formation of atherosclerotic plaques, and dysregulated energy metabolism is closely linked to the process of autophagy. However, the regulation of macrophage autophagy by pyruvate dehydrogenase (PDH), a key component of the PDH complex involved in energy and metabolic homeostasis, remains poorly understood in the context of atherosclerosis induced by Hcy. In our study, proteomic profiling identifies 748 upregulated proteins and 760 downregulated proteins in Hcy-treated macrophages. KEGG pathway analysis reveals significant enrichment of differentially expressed proteins in metabolism-related pathways, including those related to the biosynthesis of amino acids, carbon metabolism, and glycolysis/gluconeogenesis. Additionally, we explore the role of PDH in mediating Hcy-induced atherosclerosis in ApoE <sup>-/-</sup> mice. The results show a marked reduction in PDH expression and activity in Hcy-treated macrophages, leading to impaired autophagy. Notably, PDH activation enhances the assembly of the autophagy initiator ULK1-FIP200-Atg13 complex through the modulation of the AMPK/mTOR signaling pathway, suggesting a potential therapeutic target for Hcy-induced atherosclerosis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466555","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}
引用次数: 0
Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases. 代谢产物α-酮戊二酸在骨组织和骨相关疾病中的重要作用。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-19 DOI: 10.3724/abbs.2025020
Zuping Wu, Yuzhe Guan, Qian Chen, Ruifeng Song, Jing Xie, Xin Zhang, Yan Wang, Qianming Chen, Xiaoyan Chen
{"title":"Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.","authors":"Zuping Wu, Yuzhe Guan, Qian Chen, Ruifeng Song, Jing Xie, Xin Zhang, Yan Wang, Qianming Chen, Xiaoyan Chen","doi":"10.3724/abbs.2025020","DOIUrl":"https://doi.org/10.3724/abbs.2025020","url":null,"abstract":"<p><p>Bone metabolism in bone tissue is constantly maintained in a state of dynamic equilibrium. The mass of bone and joint tissues is determined by both bone formation and bone resorption. It is hypothesized that disrupted metabolic balance leads to osteoporosis, osteoarthritis, rheumatoid arthritis, and bone tumors. Such disruptions often manifest as either a reduction or abnormality in bone mass and are frequently accompanied by pathological changes such as inflammation, fractures, and pain. α-Ketoglutarate (α-KG) serves as a pivotal intermediate in various metabolic pathways in mammals, significantly contributing to cellular energy metabolism, amino acid metabolism, and other physiological processes. α-KG may be a therapeutic target for a variety of bone-related diseases, such as osteoporosis, osteoarthritis, and rheumatoid arthritis, because of its role in maintaining the metabolic balance of bone. After the application of α-KG, bone loss and inflammation in bone tissue are alleviated. This review focuses on the regulatory effects of α-KG on various cells in bone and joint tissues. Owing to the regulatory effect of α-KG on the balance of bone metabolism, the application of α-KG in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis, bone tumors, and other bone tissue diseases has been clarified.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447607","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}
引用次数: 0
Similarities and differences in the response and molecular characteristics of peripheral sensory neurons associated with pain and itch. 与疼痛和瘙痒相关的外周感觉神经元的反应和分子特征的异同。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-14 DOI: 10.3724/abbs.2024202
Li Liu, Jiemin Yin, Youqiang Meng, Congrui Ye, Junhui Chen, Sa Wang, Wen Yin, Po Gao, Yingfu Jiao, Weifeng Yu, Yinghui Fan
{"title":"Similarities and differences in the response and molecular characteristics of peripheral sensory neurons associated with pain and itch.","authors":"Li Liu, Jiemin Yin, Youqiang Meng, Congrui Ye, Junhui Chen, Sa Wang, Wen Yin, Po Gao, Yingfu Jiao, Weifeng Yu, Yinghui Fan","doi":"10.3724/abbs.2024202","DOIUrl":"https://doi.org/10.3724/abbs.2024202","url":null,"abstract":"<p><p>Dorsal root ganglion (DRG) neurons are responsible for the primary detection and transmission of peripheral noxious stimuli, mainly pain and itch. However, as two distinct noxious sensations, how DRG neurons respond differently to and code pain and itch is still an attractive topic. Here, we investigate the response and activation spectrum of DRG neurons under peripheral pain and itch stimuli using <i>in vivo</i> two-photon calcium imaging and find differences in the response intensity to pain and itch between multisensory neurons (both pain and itch) and single-sensory neurons (either pain or itch). In addition, single-cell RNA sequencing (scRNA-seq) is used to reveal the heterogeneity of distinct subpopulations on the basis of their expressions of pain- or itch-related marker genes and to determine the similarities and differences in their transcriptomic changes under chronic pain and itch. Our results show that primary sensory neurons with different sensory patterns respond differently to the same nociceptive stimuli. Additionally, distinct clusters of neurons exhibit unique transcriptomic changes in the development of chronic pain and itch, which may offer new insights for treating these conditions.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424540","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}
引用次数: 0
Tissue extracellular vesicles suppress neonatal cardiac regeneration: a Pak2-Erk1/2-mediated macrophage paracrine signaling. 组织细胞外囊泡抑制新生儿心脏再生:pak2 - erk1 /2介导的巨噬细胞旁分泌信号。
IF 3.3 2区 生物学
Acta biochimica et biophysica Sinica Pub Date : 2025-02-14 DOI: 10.3724/abbs.2024193
Yongwei Li, Laihai Zhang, Yating Wu, Lu Wei, Zhenchun Zhang, Hanling Mo, Zhongmin Liu, Xianyun Wang, Yunli Shen, Hongming Zhu
{"title":"Tissue extracellular vesicles suppress neonatal cardiac regeneration: a Pak2-Erk1/2-mediated macrophage paracrine signaling.","authors":"Yongwei Li, Laihai Zhang, Yating Wu, Lu Wei, Zhenchun Zhang, Hanling Mo, Zhongmin Liu, Xianyun Wang, Yunli Shen, Hongming Zhu","doi":"10.3724/abbs.2024193","DOIUrl":"https://doi.org/10.3724/abbs.2024193","url":null,"abstract":"<p><p>Myocardial infarction leads to cardiomyocyte loss, and the compromised proliferative capacity of cardiomyocytes after birth hinders the process of heart repair, ultimately culminating in heart failure. Extracellular vesicles (EVs), known as cell-secreted \"messengers\", play a pivotal role in tissue pathophysiology. Here, we report the novel finding that myocardial tissue-derived vesicles from mice on postnatal day 8 (P8-EVs) possess the potential to modulate cardiomyocyte proliferation. Notably, direct administration of EVs derived from day 1 or day 8 (P1/P8) myocardial tissue does not impact neonatal cardiomyocyte proliferation or myocardial repair in mice with myocardial infarction. However, by leveraging bioinformatics, high-throughput omics, and single-cell analyses, we unveil that P8-EVs are enriched with the key gene p21 activated kinase 2 (Pak2), a regulator of macrophage reparative function. Through single-cell sequencing of P8 myocardial tissue, we identify macrophages as the cell type with the highest Pak2 content, implying a close association between macrophages and P8-EV function. Intriguingly, further investigations reveal that P8-EVs significantly promote M1-like polarization, augment phagocytosis, and affect factor secretion in macrophages. Co-culture experiments demonstrate that P8-EV-treated macrophages strongly suppress neonatal cardiomyocyte proliferation, and this effect is effectively reversed by a Pak2 inhibitor. Additional pathway intervention experiments reveal that P8-EVs activate the downstream Erk1/2 signaling pathway of Pak2. Collectively, our findings indicate that P8-EVs regulate macrophage paracrine activities through the Pak2-Erk1/2 axis, thereby influencing cardiomyocyte proliferation. This finding reveals a potential underlying mechanism for the compromised proliferative capacity of cardiomyocytes in adult mice.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412755","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}
引用次数: 0
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