Protein & CellPub Date : 2025-08-20DOI: 10.1093/procel/pwaf062
Zimu Tang, Zhaoxiang Sun, Chun Yang, Qian Gong, Zirui Liu, Nanhui Chen, Kai Liu, Yong Wang, Ting Zhao, Shengfan Ye, Lenan Zhuang, Jiahao Lin, Wei-Qiang Tan, Jinrong Peng, Jun Chen
{"title":"Accumulation of newly synthesized docosahexaenoic acid plays an essential role in heart regeneration.","authors":"Zimu Tang, Zhaoxiang Sun, Chun Yang, Qian Gong, Zirui Liu, Nanhui Chen, Kai Liu, Yong Wang, Ting Zhao, Shengfan Ye, Lenan Zhuang, Jiahao Lin, Wei-Qiang Tan, Jinrong Peng, Jun Chen","doi":"10.1093/procel/pwaf062","DOIUrl":"https://doi.org/10.1093/procel/pwaf062","url":null,"abstract":"<p><p>Adult zebrafish and neonatal mice can fully regenerate their hearts after partial amputation through proliferation of pre-existing cardiomyocytes (CMs). However, the adult mammalian heart has limited regenerative capability following cardiac damage. The reason for this phenomenon remains elusive. Here, we find that docosahexaenoic acid (DHA) is accumulated only in the injury hearts of zebrafish and neonatal mice, but not of adult mice, which coincides with the upregulation of DHA synthesis genes in CMs, fibrobasts and macrophages near the injury areas. Inhibition of Fads2, a DHA synthesis enzyme, impairs heart regeneration in both zebrafish and neonatal mice. Injection of DHA remodels transcriptome from injury response to regeneration response and improves cardiac function in adult mice after myocardial infarction. Interestingly, DHA facilitates CM proliferation, but inhibits fibrosis and inflammation. Mechanistically, only DHA, but not oleic acid (OA), can trigger the peroxisome proliferator-activated receptor d (PPARD) to bind to the promoter regions of heart regeneration related genes such as: Mef2d, Phlda3 and Txndc5 to regulate their expression. Molecular docking, molecular dynamics simulations and mutagenesis experiments suggest that DHA binds to PPARD in a distinct manner compared to OA, which may help explain their differing abilities to influence the expression of heart regeneration genes. Our findings demonstrate that the DHA signal plays an essential and evolutionarily conserved role in heart regeneration and provide a therapeutic potential for myocardial infarction.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966436","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":"Accumulation of newly synthesized docosahexaenoic acid plays an essential role in heart regeneration.","authors":"Zimu Tang,Zhaoxiang Sun,Chun Yang,Qian Gong,Zirui Liu,Nanhui Chen,Kai Liu,Yong Wang,Ting Zhao,Shengfan Ye,Lenan Zhuang,Jiahao Lin,Wei-Qiang Tan,Jinrong Peng,Jun Chen","doi":"10.1093/procel/pwaf062","DOIUrl":"https://doi.org/10.1093/procel/pwaf062","url":null,"abstract":"Adult zebrafish and neonatal mice can fully regenerate their hearts after partial amputation through proliferation of pre-existing cardiomyocytes (CMs). However, the adult mammalian heart has limited regenerative capability following cardiac damage. The reason for this phenomenon remains elusive. Here, we find that docosahexaenoic acid (DHA) is accumulated only in the injury hearts of zebrafish and neonatal mice, but not of adult mice, which coincides with the upregulation of DHA synthesis genes in CMs, fibrobasts and macrophages near the injury areas. Inhibition of Fads2, a DHA synthesis enzyme, impairs heart regeneration in both zebrafish and neonatal mice. Injection of DHA remodels transcriptome from injury response to regeneration response and improves cardiac function in adult mice after myocardial infarction. Interestingly, DHA facilitates CM proliferation, but inhibits fibrosis and inflammation. Mechanistically, only DHA, but not oleic acid (OA), can trigger the peroxisome proliferator-activated receptor d (PPARD) to bind to the promoter regions of heart regeneration related genes such as: Mef2d, Phlda3 and Txndc5 to regulate their expression. Molecular docking, molecular dynamics simulations and mutagenesis experiments suggest that DHA binds to PPARD in a distinct manner compared to OA, which may help explain their differing abilities to influence the expression of heart regeneration genes. Our findings demonstrate that the DHA signal plays an essential and evolutionarily conserved role in heart regeneration and provide a therapeutic potential for myocardial infarction.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"71 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959928","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":"MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.","authors":"Bao Xue, Anqi Zhou, Yihang Zhong, Yuhan Mao, Ran Peng, Yuhang Chen, Jiayi Zhong, Junjun Liu, Yuan Zhou, Yuying Fang, Wei Zhang, Jielin Tang, Wei Peng, Jia Liu, Qi Yang, Xinwen Chen","doi":"10.1093/procel/pwaf063","DOIUrl":"https://doi.org/10.1093/procel/pwaf063","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) exploits host proteases to enhance its replication efficiency; however, the precise mechanisms remain unclear. Through high-throughput screening, we identified four matrix metalloproteinase 9 (MMP-9) inhibitors (including JNJ0966 and doxycycline hyclate) that suppress RSV infection in vitro and in vivo. Mechanistic studies revealed a proteolytic cascade wherein MMP-9 cleaves transglutaminase 2 (TGM2) at the PVP375↓VR site, generating an N-terminal fragment (1-375) that activates its protein disulfide isomerase (PDI) activity. This TGM2-dependent PDI activity catalyzes disulfide bond rearrangement in the RSV fusion glycoprotein (F), enabling F protein maturation, a prerequisite for membrane fusion and syncytium formation-key processes driving late-stage viral propagation. Genetic ablation of MMP-9 significantly attenuated RSV infectivity, while pharmacological inhibition reduced pulmonary viral loads and mitigated lung pathology in infected mice. Our study defines a unified MMP-9→TGM2→F axis as the core mechanism driving RSV replication and validates MMP-9 as a therapeutic target.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848529","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":"Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation.","authors":"Xuyang Wang, Ruoqi Cheng, Chenyang Wu, Haiyin Liu, Zining Li, Yunfei Huo, Bo Li, Dongyu Zhao, Cheng Li, Hongkui Deng, Jun Xu","doi":"10.1093/procel/pwaf059","DOIUrl":"https://doi.org/10.1093/procel/pwaf059","url":null,"abstract":"<p><p>Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells. These cells retain trophectoderm-specific transcriptomic features and can differentiate into trophoblast lineages in vivo. Moreover, combining these trophectoderm-like cells with EPS cell-derived primitive endoderm/epiblast bilineage structures enabled the robust generation of post-implantation embryoids in a transgene-free manner. EPS-derived embryoids recapitulate key developmental events of post-implantation mouse embryos, including the formation of the pro-amniotic cavity, anterior-posterior axis, primitive streak, gastrulation, and complex extraembryonic tissues. Notably, single-cell transcriptomic analysis revealed a high degree of transcriptional similarity between EPS-derived embryoids at day 6 and natural E7.5 mouse embryos. Our study presents a novel platform for modeling post-implantation mouse embryogenesis in vitro.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848530","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
