Journal of Molecular Cell Biology最新文献_第6页

HSD17B13 liquid–liquid phase separation promotes leukocyte adhesion in chronic liver inflammation HSD17B13液-液相分离促进慢性肝脏炎症中的白细胞粘附

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-05-02 DOI: 10.1093/jmcb/mjae018

Jing Ye, Xiyu Huang, Manman Yuan, Jinglin Wang, Ru Jia, Tianyi Wang, Yang Tan, Shun Zhu, Qiang Xu, Xingxin Wu

{"title":"HSD17B13 liquid–liquid phase separation promotes leukocyte adhesion in chronic liver inflammation","authors":"Jing Ye, Xiyu Huang, Manman Yuan, Jinglin Wang, Ru Jia, Tianyi Wang, Yang Tan, Shun Zhu, Qiang Xu, Xingxin Wu","doi":"10.1093/jmcb/mjae018","DOIUrl":"https://doi.org/10.1093/jmcb/mjae018","url":null,"abstract":"The rs72613567:TA polymorphism in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) has been found to reduce the progression from steatosis to nonalcoholic steatohepatitis. In this study, we sought to define the pathogenic role of HSD17B13 in triggering liver inflammation. Here we find that HSD17B13 forms liquid–liquid phase separation (LLPS) around lipid droplets in the livers of nonalcoholic steatohepatitis patients. The dimerization of HSD17B13 supports the LLPS formation and promotes its enzymatic function. HSD17B13 LLPS increases the biosynthesis of platelet activating factor (PAF), which in turn promotes fibrinogen synthesis and leukocyte adhesion. Blockade of PAFR or STAT3 pathway inhibited the fibrinogen synthesis and leukocyte adhesion. Importantly, adeno-associated viral-mediated xeno-expression of human HSD17B13 exacerbated western diet/carbon tetrachloride-induced liver inflammation in Hsd17b13−/− mice. In conclusion, our results suggest that HSD17B13 LLPS triggers liver inflammation by promoting PAF-mediated leukocyte adhesion, and targeting HSD17B13 phase transition could be a promising therapeutic approach for treating hepatic inflammation in chronic liver disease.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840328","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

Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction. 化学诱导下小鼠成纤维细胞高效转化为功能性肝细胞。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad071

Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang

{"title":"Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction.","authors":"Zhi Zhong, Jiangchuan Du, Xiangjie Zhu, Lingting Guan, Yanyu Hu, Peilin Zhang, Hongyang Wang","doi":"10.1093/jmcb/mjad071","DOIUrl":"10.1093/jmcb/mjad071","url":null,"abstract":"Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods. However, these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes. In this study, we present a transgene-free, highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts (MEFs). Using a small molecule cocktail (SMC) as an inducer, MEFs can be directly reprogrammed into hepatocyte-like cells, bypassing the intermediate stages of pluripotent and immature hepatoblasts. These chemical-induced hepatocyte-like cells (ciHeps) closely resemble mature primary hepatocytes in terms of morphology, biological behavior, gene expression patterns, marker expression levels, and hepatic functions. Furthermore, transplanted ciHeps can integrate into the liver, promote liver regeneration, and improve survival rates in mice with acute liver damage. ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function. Notably, ciHeps exhibit no tumorigenic potential either in vitro or in vivo. Mechanistically, SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps. These results indicate that this transgene-free, chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes. Additionally, this method also sheds light on the direct reprogramming of other cell types under chemical induction.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11121195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299267","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

A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex. 针对SMAD4-SMAD3-DNA复合物的多路时间分辨荧光共振能量转移超高通量筛选试验

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad068

Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo

{"title":"A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex.","authors":"Wukun Ouyang, Qianjin Li, Qiankun Niu, Min Qui, Haian Fu, Yuhong Du, Xiulei Mo","doi":"10.1093/jmcb/mjad068","DOIUrl":"10.1093/jmcb/mjad068","url":null,"abstract":"The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule inhibitors specifically targeting SMAD4, the downstream master regulator of the TGFβ pathway, would offer an alternative approach with significant therapeutic potential for anti-TGFβ signaling. In this study, we present the development of a cell lysate-based multiplexed time-resolved fluorescence resonance energy transfer (TR-FRET) assay in an ultrahigh-throughput screening (uHTS) 1536-well plate format. This assay enables simultaneous monitoring of the protein‒protein interaction between SMAD4 and SMAD3, as well as the protein‒DNA interaction between SMADs and their consensus DNA-binding motif. The multiplexed TR-FRET assay exhibits high sensitivity, allowing the dynamic analysis of the SMAD4-SMAD3-DNA complex at single-amino acid resolution. Moreover, the multiplexed uHTS assay demonstrates robustness for screening small-molecule inhibitors. Through a pilot screening of an FDA-approved bioactive compound library, we identified gambogic acid and gambogenic acid as potential hit compounds. These proof-of-concept findings underscore the utility of our optimized multiplexed TR-FRET platform for large-scale screening to discover small-molecule inhibitors that target the SMAD4-SMAD3-DNA complex as novel anti-TGFβ signaling agents.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649204","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

Derivation of zebrafish heart-related haploid cells. 斑马鱼心脏相关单倍体细胞的衍生。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad077

Siqi Liu, Jia Xu, Yirui Ai, Yunbin Zhang, Shifeng Li, Jinsong Li, Yiping Li

引用次数: 0

Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study. 腹部脂肪与非酒精性脂肪肝之间的性别和年龄特异性关联:一项前瞻性队列研究

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad069

Hongli Chen, Yuexing Liu, Dan Liu, Yebei Liang, Zhijun Zhu, Keqing Dong, Huating Li, Yuqian Bao, Jiarui Wu, Xuhong Hou, Weiping Jia

{"title":"Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study.","authors":"Hongli Chen, Yuexing Liu, Dan Liu, Yebei Liang, Zhijun Zhu, Keqing Dong, Huating Li, Yuqian Bao, Jiarui Wu, Xuhong Hou, Weiping Jia","doi":"10.1093/jmcb/mjad069","DOIUrl":"10.1093/jmcb/mjad069","url":null,"abstract":"Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years. During a 4.6-year median follow-up, the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females. Further analyses showed that the above-mentioned positive associations were stronger in males than in females, especially in participants under 60 years old. In contrast, these sex differences disappeared in those over 60 years old. Furthermore, the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern. Additionally, sex-specific potential mediators, such as insulin resistance, lipid metabolism, inflammation, and adipokines, may exist in the associations between adipose tissue and NAFLD. This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age, highlighting the potential need for sex- and age-specific management of NAFLD.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460469","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

Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy. 靶向PD-L1细胞质结构域及其调控途径增强癌症免疫治疗。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad070

Fangni Chai, Pan Li, Xin Liu, Zhihui Zhou, Haiyan Ren

{"title":"Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy.","authors":"Fangni Chai, Pan Li, Xin Liu, Zhihui Zhou, Haiyan Ren","doi":"10.1093/jmcb/mjad070","DOIUrl":"10.1093/jmcb/mjad070","url":null,"abstract":"As a significant member of the immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) plays a critical role in cancer immune escape and has become an important target for cancer immunotherapy. Clinically approved drugs mainly target the extracellular domain of PD-L1. Recently, the small cytoplasmic domain of PD-L1 has been reported to regulate PD-L1 stability and function through multiple pathways. Therefore, the intracellular domain of PD-L1 and its regulatory pathways could be promising targets for cancer therapy, expanding available strategies for combined immunotherapy. Here, we summarize the emerging roles of the PD-L1 cytoplasmic domain and its regulatory pathways. The conserved motifs, homodimerization, and posttranslational modifications of the PD-L1 cytoplasmic domain have been reported to regulate the membrane anchoring, degradation, nuclear translocation, and glycosylation of PD-L1. This summary provides a comprehensive understanding of the functions of the PD-L1 cytoplasmic domain and evaluates the broad prospects for targeted therapy.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295336","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

JunB condensation attenuates vascular endothelial damage under hyperglycemic condition. JunB 缩合可减轻高血糖条件下的血管内皮损伤。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad072

Xuxia Ren, Zexu Cui, Qiaoqiao Zhang, Zhiguang Su, Wei Xu, Jinhui Wu, Hao Jiang

引用次数: 0

The interplay between the muscle and liver in the regulation of glucolipid metabolism. 肌肉和肝脏在调节糖脂代谢中的相互作用。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad073

Cheng Chen, Liping Xie, Mingliang Zhang, Shama, Kenneth King Yip Cheng, Weiping Jia

引用次数: 0

The capsid revolution. 衣壳革命。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad076

Ian A Taylor, Ariberto Fassati

引用次数: 0

Glycogen synthase kinase 3 signaling in neural regeneration in vivo. 糖原合成酶激酶3信号在体内神经再生中的作用。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-10 DOI: 10.1093/jmcb/mjad075

Jing Zhang, Shu-Guang Yang, Feng-Quan Zhou

{"title":"Glycogen synthase kinase 3 signaling in neural regeneration in vivo.","authors":"Jing Zhang, Shu-Guang Yang, Feng-Quan Zhou","doi":"10.1093/jmcb/mjad075","DOIUrl":"10.1093/jmcb/mjad075","url":null,"abstract":"Glycogen synthase kinase 3 (GSK3) signaling plays important and broad roles in regulating neural development in vitro and in vivo. Here, we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the field. Overall, current evidence indicates that GSK3β signaling serves as an important downstream mediator of the PI3K-AKT pathway to regulate axon regeneration in parallel with the mTORC1 pathway. Specifically, the mTORC1 pathway supports axon regeneration mainly through its role in regulating cap-dependent protein translation, whereas GSK3β signaling might be involved in regulating N6-methyladenosine mRNA methylation-mediated, cap-independent protein translation. In addition, GSK3 signaling also plays a key role in reshaping the neuronal transcriptomic landscape during neural regeneration. Finally, we proposed some research directions to further elucidate the molecular mechanisms underlying the regulatory function of GSK3 signaling and discover novel GSK3 signaling-related therapeutic targets. Together, we hope to provide an updated and insightful overview of how GSK3 signaling regulates neural regeneration in vivo.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498637","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