Protein & Cell最新文献

Indole-3-propionic acid is an endogenic agonist of hypoxia-inducible factor-1α to protect the heart against hypoxia. 吲哚-3-丙酸是一种内源性的缺氧诱导因子-1α激动剂，具有保护心脏免受缺氧的作用。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-04 DOI: 10.1093/procel/pwag067

Ziang Zhang, Sen Yu, Yuan Xing, Pengfei Zhang, Han Li, Min Li, Shichao Sun, Zihang Feng, Lulu Gong, Xiangyang Qin, Zhihui Feng, Jia Li, Xinghua Qin, Yong Liu, Feng Gao, Xing Zhang

{"title":"Indole-3-propionic acid is an endogenic agonist of hypoxia-inducible factor-1α to protect the heart against hypoxia.","authors":"Ziang Zhang, Sen Yu, Yuan Xing, Pengfei Zhang, Han Li, Min Li, Shichao Sun, Zihang Feng, Lulu Gong, Xiangyang Qin, Zhihui Feng, Jia Li, Xinghua Qin, Yong Liu, Feng Gao, Xing Zhang","doi":"10.1093/procel/pwag067","DOIUrl":"https://doi.org/10.1093/procel/pwag067","url":null,"abstract":"Tryptophan catabolism by the gut microbiota is increasingly recognized as a hub connecting environmental challenges to cardiovascular health. By systematically profiling tryptophan metabolites in humans who had moved from low altitude to an altitude of 4300 m and in mice exposed to hypobaric hypoxia, we found that circulating and fecal levels of indole-3-propionic acid (IPA), a gut microbiota-derived tryptophan metabolite, are reduced in both settings, and these reductions correlate with the severity of cardiac injury. IPA supplementation in mice ameliorated hypobaric hypoxia-induced cardiac dysfunction. Mechanistically, IPA directly bound to hypoxia-inducible factor-1α (HIF-1α) at residue P564, competitively inhibiting its interaction with von Hippel-Lindau protein and preventing proteasomal degradation, thereby stabilizing HIF-1α. HIF-1α activation shifted cardiac metabolic substrate utilization from fatty acids to glucose and reduced oxygen consumption. Cardiomyocyte-specific HIF-1α knockout completely abolished IPA's cardioprotective effects. Moreover, gut microbiota depletion abrogated the protective effect of tryptophan against hypobaric hypoxia exposure. Finally, IPA protected against myocardial infarction in a HIF-1α-dependent manner. These results suggest that IPA is an endogenous HIF-1α agonist to protect the heart against hypoxia/ischemia, representing a promising therapeutic candidate for hypoxic/ischemic diseases.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":18.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892358","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

A Dual role of alveolar macrophage in driving host defense and pulmonary immunopathology during hypervirulent Acinetobacter baumannii pneumonia. 高毒力鲍曼不动杆菌肺炎期间肺泡巨噬细胞在驱动宿主防御和肺免疫病理中的双重作用。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-04 DOI: 10.1093/procel/pwag066

Duo Su, Yan Wang, Lu Li, Jin Zhao, Lingfei Hu, Wenhui Yang, Bo Yang, Jie Zhang, Huiying Yang, Dongsheng Zhou

{"title":"A Dual role of alveolar macrophage in driving host defense and pulmonary immunopathology during hypervirulent Acinetobacter baumannii pneumonia.","authors":"Duo Su, Yan Wang, Lu Li, Jin Zhao, Lingfei Hu, Wenhui Yang, Bo Yang, Jie Zhang, Huiying Yang, Dongsheng Zhou","doi":"10.1093/procel/pwag066","DOIUrl":"https://doi.org/10.1093/procel/pwag066","url":null,"abstract":"Hypervirulent Acinetobacter baumannii (hvAB) is a leading cause of refractory bacterial pneumonia. However, cellular and molecular mechanisms underlying hvAB-induced host protection and pulmonary immunopathology remain poorly understood. Here, we performed longitudinal single-cell RNA sequencing on lung tissues in a mouse model of hvAB pneumonia and delineated a time-dependent innate immune landscape of the infected lung. Functional experiments demonstrated that neutrophil (Neu) was dispensable for hvAB clearance but exacerbated acute lung injury through Neu extracellular traps formation (NETosis). Lung-resident CD11b- alveolar macrophage (AM) was indispensable for host defense and for restraining early Neu infiltration. Upon hvAB infection, CD11b- AM underwent phenotypic switching to a hyper-activated CD11b+ pro-inflammatory state, characterized by markedly decreased phagocytic activity and robustly enhanced IL-1β secretion. Mechanistically, IL-17A acted as a key pathogenic mediator by driving excessive Neu recruitment, aberrant NETosis, and progressive AM loss. IL-17A was predominantly produced by group 3 innate lymphoid cell (ILC3) in an IL-1β-dependent manner. Collectively, our study defined a critical pathogenic AM-ILC3-Neu axis and highlighted a paradoxical dual role of AM in driving host defense and pulmonary immunopathology through dynamic phenotypic switching. We suggested that targeting AM phenotypic plasticity represented a promising therapeutic strategy to alleviate excessive immunopathology while preserving protective host defense during hvAB pneumonia.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":18.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892340","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

Guanine promotes acute lung injury by repressing H3K27me3 in sepsis. 鸟嘌呤通过抑制败血症中的H3K27me3促进急性肺损伤。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-03 DOI: 10.1093/procel/pwag065

Chao-Qun Wang, Hui-Juan Wang, Yue-Yu Kong, Xiayila Abulaiti, Xiao-Hui Zhang, Liu Liu, Rui-Feng Shi, Sheng Hu, Xu Li, Mei-Xin Li, Lu Wang, Jia-Xi Lei, Jing Zhang, Li-Min Xiang, Long-Fei Wang, Tao Long, Hai-Ning Du, Li-Ying Zhan, Wei Yan

{"title":"Guanine promotes acute lung injury by repressing H3K27me3 in sepsis.","authors":"Chao-Qun Wang, Hui-Juan Wang, Yue-Yu Kong, Xiayila Abulaiti, Xiao-Hui Zhang, Liu Liu, Rui-Feng Shi, Sheng Hu, Xu Li, Mei-Xin Li, Lu Wang, Jia-Xi Lei, Jing Zhang, Li-Min Xiang, Long-Fei Wang, Tao Long, Hai-Ning Du, Li-Ying Zhan, Wei Yan","doi":"10.1093/procel/pwag065","DOIUrl":"https://doi.org/10.1093/procel/pwag065","url":null,"abstract":"Sepsis is systemic inflammation with high mortality, accompanied by multi-organ failure including acute respiratory distress syndrome. Extracellular vesicles (EVs) encapsulating bioactive cargoes, mediate cell-cell communication to exert systemic regulation. However, whether and how host lung tissue responds quickly to plasma bacterial infection through EVs in sepsis is poorly understood. Here, we identify that peripheral blood macrophages secrete more exosomal G6PD protein to induce lung injury by rewiring purine metabolism during sepsis. Guanine accumulation reduces H3K27 trimethylation and subsequently induces Nos2, Ccl6 and Il6 expression by suppressing de novo EZH2 synthesis. Macrophage-specific Rab27a or G6pd knockout mice had low exosomal G6PD protein in serum, and failed to exert lung injury upon bacterial infection. Beyond, targeting macrophage-derived G6PD by G6PD inhibitors or engineered EVs delivering si-G6pd relieves lung injury in septic mice. In summary, our findings reveal that circulating G6PD promotes lung injury by rewiring purine metabolism and remodeling the epigenetic profile in sepsis, shedding light on the critical role of EVs as a pro-inflammatory signal and targeting G6PD for future sepsis diagnosis and treatment.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":18.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888401","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

Molecular virulence mechanism of phospholipase C from Pseudomonas aeruginosa. 铜绿假单胞菌磷脂酶C的分子毒力机制。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-01 DOI: 10.1093/procel/pwag062

Nishika Sabharwal, Yang Ge, Michele Lunelli, Udom Sae-Ueng, Cy M Jeffries, Spyros Chatziefthymiou, Sukrit Srivastava, Aziz Tumeh, Andre Geisler, Michael Kolbe, Jörg Labahn

引用次数: 0

DNA-triggered AIM2 condensation orchestrates immune activation and regulation. dna触发的AIM2缩合协调免疫激活和调节。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-01 DOI: 10.1093/procel/pwag024

Quanjin Li, Xiaohan Geng, Huiwen Yan, Zhaolong Li, Miao Shi, Ziqi Zhu, Tongxin Niu, Chunqiu Zhao, Kaile Shu, Yina Gao, Han Feng, Songqing Liu, Qiuyao Jiang, Pengcheng Bu, Dong Li, Pu Gao

{"title":"DNA-triggered AIM2 condensation orchestrates immune activation and regulation.","authors":"Quanjin Li, Xiaohan Geng, Huiwen Yan, Zhaolong Li, Miao Shi, Ziqi Zhu, Tongxin Niu, Chunqiu Zhao, Kaile Shu, Yina Gao, Han Feng, Songqing Liu, Qiuyao Jiang, Pengcheng Bu, Dong Li, Pu Gao","doi":"10.1093/procel/pwag024","DOIUrl":"10.1093/procel/pwag024","url":null,"abstract":"The innate immune sensor AIM2 detects cytosolic DNA and initiates inflammatory responses, yet its activation mechanism remains incompletely understood. Here, we show that AIM2 undergoes liquid-liquid phase separation upon DNA binding, forming dynamic condensates both in vitro and in cells. These condensates serve as platforms for inflammasome and PANoptosome assembly, promoting immune activation across multiple pathways. Direct structural determination from condensates reveals the assembly of active-form ASC filaments. Mechanistically, liquid-phase condensation is governed by multivalent interactions involving different AIM2 domains, including previously uncharacterized regions and species-specific elements. In vitro and in vivo assays show that mutants specifically disrupting condensation impair immune complex assembly, cell death initiation, antimicrobial defense, and intestinal homeostasis. Moreover, AIM2-DNA condensates function as regulatory hubs targeted by host- and pathogen-derived factors to balance immune homeostasis or facilitate immune evasion. These findings establish liquid-phase condensation as a fundamental mechanism of AIM2 activation and a potential therapeutic target.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"807-820"},"PeriodicalIF":18.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Restoring the FOXO1 geroprotective pathway via seno-resistant mesenchymal progenitor cells alleviates primate epididymal aging. 通过抗衰老间充质祖细胞恢复FOXO1衰老保护通路可减轻灵长类附睾衰老。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-01 DOI: 10.1093/procel/pwag020

Huifen Lu, Linguo Cai, DongLiang Lv, Guoqiang Sun, Jinghui Lei, Taixin Ning, Zijuan Xin, Haoyan Huang, Ying Jing, Daoyuan Huang, Shuhui Sun, Shuai Ma, Weiqi Zhang, Fei Gao, Rui Chen, Yingying Qin, Weihong Song, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang

{"title":"Restoring the FOXO1 geroprotective pathway via seno-resistant mesenchymal progenitor cells alleviates primate epididymal aging.","authors":"Huifen Lu, Linguo Cai, DongLiang Lv, Guoqiang Sun, Jinghui Lei, Taixin Ning, Zijuan Xin, Haoyan Huang, Ying Jing, Daoyuan Huang, Shuhui Sun, Shuai Ma, Weiqi Zhang, Fei Gao, Rui Chen, Yingying Qin, Weihong Song, Andy Peng Xiang, Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Jing Qu, Si Wang","doi":"10.1093/procel/pwag020","DOIUrl":"10.1093/procel/pwag020","url":null,"abstract":"Aging of the male reproductive system is characterized by declining fertility, with epididymal dysfunction being a critical yet poorly understood contributor. Through a multimodal analysis in non-human primates that integrated histology and transcriptomics, we delineated a coherent epididymal aging phenotype encompassing epithelial senescence, chronic inflammation, fibrosis, and functional decline. Single-nucleus transcriptomics revealed principal cells (PCs) as the predominant and most transcriptionally perturbed epithelial cell type. Within PCs, the longevity-associated transcription factor FOXO1 was markedly downregulated with age. Functional studies in human epididymal epithelial cells demonstrated that FOXO1 deficiency drives cellular senescence. Mechanistically, FOXO1 transcriptionally activates LHX1, and this axis is essential for counteracting senescence. Furthermore, intervention with senescence-resistant mesenchymal progenitor cells or their exosomes mitigated epididymal aging phenotypes and restored FOXO1 expression in vivo and in vitro. Our study establishes the FOXO1-LHX1 axis as a key protective pathway against primate epididymal aging, providing mechanistic insights and potential therapeutic targets for preserving male reproductive health.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"840-857"},"PeriodicalIF":18.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Correction to: Skin organoid transplantation promotes tissue repair with scarless in frostbite. 纠正：皮肤类器官移植促进冻伤组织修复无瘢痕。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-09-01 DOI: 10.1093/procel/pwag001

引用次数: 0

Correction to: Multi-omics analysis reveals comprehensive aberrant protein and phosphorylation characteristics in breast cancer and paired metastatic lymph nodes. 更正：多组学分析揭示了乳腺癌和配对转移性淋巴结中全面的异常蛋白和磷酸化特征。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-08-28 DOI: 10.1093/procel/pwag055

引用次数: 0

LMNA R527C pathogenic variant causes an inflammation-driven segmental progeroid syndrome via triggering DNA-sensing pathways. LMNA R527C致病性变异通过触发dna传感途径引起炎症驱动的节段性类早衰综合征。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-08-25 DOI: 10.1093/procel/pwag061

Yingchi Zhao, Tianyi Liu, Wei Shu, Dandan Wang, Haocheng Wang, Xiaoyu Liu, Xuyao Jiao, Jianshuang Li, Tao Liu, Ming Kuang, Ridong Li, Hongqiang Du, Zeming Zhang, Zhe Zhou, Xuefei Guo, Xuemei Wei, Tongtong Liu, Yunfei Li, Shengde Liu, Jingxuan Chen, Yujie Luo, Huawei Xia, Lili Cao, Wenmin Tian, Xue Sun, Wei Dong, Guangqian Zhou, Xiang Gao, Yongzhi Li, Shize Liu, Xinran Liu, Dan Lu, Qinghua Zhou, Pingsen Zhao, Fuping You

{"title":"LMNA R527C pathogenic variant causes an inflammation-driven segmental progeroid syndrome via triggering DNA-sensing pathways.","authors":"Yingchi Zhao, Tianyi Liu, Wei Shu, Dandan Wang, Haocheng Wang, Xiaoyu Liu, Xuyao Jiao, Jianshuang Li, Tao Liu, Ming Kuang, Ridong Li, Hongqiang Du, Zeming Zhang, Zhe Zhou, Xuefei Guo, Xuemei Wei, Tongtong Liu, Yunfei Li, Shengde Liu, Jingxuan Chen, Yujie Luo, Huawei Xia, Lili Cao, Wenmin Tian, Xue Sun, Wei Dong, Guangqian Zhou, Xiang Gao, Yongzhi Li, Shize Liu, Xinran Liu, Dan Lu, Qinghua Zhou, Pingsen Zhao, Fuping You","doi":"10.1093/procel/pwag061","DOIUrl":"https://doi.org/10.1093/procel/pwag061","url":null,"abstract":"Homozygous pathogenic variants in Ig-like domain of LMNA cause severe segmental progeroid syndromes. Unlike typical HGPS, it remains elusive how these pathogenic variants cause segmental progeroid syndromes. We here reported that affected individuals with LMNAR527C/R527C pathogenic variant developed an atypical segmental progeroid syndrome characterized by autoimmune features. Mesenchymal stem cells (MSCs) derived from these affected individuals exhibited significant inflammation and cellular senescence. In mice, LmnaR527C/R527C pathogenic variant triggered chronic interferon signaling, exacerbated aging-related pathologies, and even induced thymic lymphomas following ionizing radiation. In addition, this pathogenic variant increased susceptibility to inflammation induced by a high-fat diet or LCMV infection. R527C pathogenic variant disrupted the interaction between Lamin A and DNA-binding proteins, causing abnormal protein aggregation and hyperactivation of the cGAS-STING. Importantly, blocking DNA sensing pathways suppressed inflammation, rescued senescence in affected individual-derived MSCs, and alleviated premature aging in LmnaR527C/R527C mice. These findings establish a homozygous LMNA pathogenic variant as a key driver of inflammation-driven segmental progeroid syndrome and highlight DNA sensing pathways as promising therapeutic targets.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":18.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819200","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

Adaptor proteins recruit DRP1 into helical assemblies on mitochondria: Insights from super-resolution imaging. 衔接蛋白将DRP1招募到线粒体的螺旋装配中：来自超分辨率成像的见解。

IF 18.2 1区生物学

Protein & Cell Pub Date : 2026-08-25 DOI: 10.1093/procel/pwag058

Xian'ao Zhao, Shihang Luo, Yuanyuan Zhou, Tianying Pan, Shuanglei Li, Shuai Zhou, Ke Xiao, Tianjie Yang, Ran Gong, Mingcong Zhang, Jingjing Zhang, Weixing Li, Lusheng Gu, Tao Xu, Wei Ji

引用次数: 0