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CX3CL1-CX3CR1 axis protects retinal ganglion cells by inhibiting microglia activation in a distal optic nerve trauma model 在视神经远端创伤模型中,CX3CL1-CX3CR1 轴通过抑制小胶质细胞的激活保护视网膜神经节细胞
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2024-06-06 DOI: 10.1186/s41232-024-00343-4
Huan Yu, Bingqiao Shen, Ruiqi Han, Yang Zhang, Shushu Xu, Yumeng Zhang, Yanzhi Guo, Ping Huang, Shouyue Huang, Yisheng Zhong
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引用次数: 0
Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration Emilin2 标志着骨再生过程中间质细胞聚集的目标区域
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2024-06-03 DOI: 10.1186/s41232-024-00341-6
Yifan Qing, T. Ono, Y. Kohara, Atsushi Watanabe, Noboru Ogiso, Masako Ito, Tomoki Nakashima, Sunao Takeshita
{"title":"Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration","authors":"Yifan Qing, T. Ono, Y. Kohara, Atsushi Watanabe, Noboru Ogiso, Masako Ito, Tomoki Nakashima, Sunao Takeshita","doi":"10.1186/s41232-024-00341-6","DOIUrl":"https://doi.org/10.1186/s41232-024-00341-6","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141228499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of cellular senescence in inflammation and regeneration 细胞衰老在炎症和再生中的作用
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2024-06-03 DOI: 10.1186/s41232-024-00342-5
Yuki Saito, Sena Yamamoto, Takako S. Chikenji
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引用次数: 0
Th22 is the effector cell of thymosin β15-induced hair regeneration in mice Th22 是胸腺肽 β15 诱导小鼠毛发再生的效应细胞
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2024-01-08 DOI: 10.1186/s41232-023-00316-z
Nana Tao, Yuyuan Ying, Xie Xu, Qingru Sun, Yaoying Shu, Shiyu Hu, Zhaohuan Lou, Jianli Gao
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引用次数: 0
The gut-liver axis in hepatobiliary diseases 肝胆疾病中的肠肝轴
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2024-01-08 DOI: 10.1186/s41232-023-00315-0
Masataka Ichikawa, Haruka Okada, N. Nakamoto, N. Taniki, Po-sung Chu, Takanori Kanai
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引用次数: 0
Unveiling dynamic interactions: in vivo imaging chronicles inflammation and regeneration in living organisms 揭示动态相互作用:活体成像记录生物体的炎症和再生过程
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1186/s41232-023-00312-3
K. Kabashima
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引用次数: 0
Inter-organ communication involved in metabolic regulation at the whole-body level 全身代谢调节所涉及的器官间交流
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2023-12-01 DOI: 10.1186/s41232-023-00306-1
Hideki Katagiri
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引用次数: 0
A disease-specific iPS cell resource for studying rare and intractable diseases. 一种用于研究罕见和难治性疾病的疾病特异性iPS细胞资源。
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2023-09-08 DOI: 10.1186/s41232-023-00294-2
Megumu K Saito, Mitsujiro Osawa, Nao Tsuchida, Kotaro Shiraishi, Akira Niwa, Knut Woltjen, Isao Asaka, Katsuhisa Ogata, Suminobu Ito, Shuzo Kobayashi, Shinya Yamanaka

Background: Disease-specific induced pluripotent stem cells (iPSCs) are useful tools for pathological analysis and diagnosis of rare diseases. Given the limited available resources, banking such disease-derived iPSCs and promoting their widespread use would be a promising approach for untangling the mysteries of rare diseases. Herein, we comprehensively established iPSCs from patients with designated intractable diseases in Japan and evaluated their properties to enrich rare disease iPSC resources.

Methods: Patients with designated intractable diseases were recruited for the study and blood samples were collected after written informed consent was obtained from the patients or their guardians. From the obtained samples, iPSCs were established using the episomal method. The established iPSCs were deposited in a cell bank.

Results: We established 1,532 iPSC clones from 259 patients with 139 designated intractable diseases. The efficiency of iPSC establishment did not vary based on age and sex. Most iPSC clones originated from non-T and non-B hematopoietic cells. All iPSC clones expressed key transcription factors, OCT3/4 (range 0.27-1.51; mean 0.79) and NANOG (range 0.15-3.03; mean 1.00), relative to the reference 201B7 iPSC clone.

Conclusions: These newly established iPSCs are readily available to the researchers and can prove to be a useful resource for research on rare intractable diseases.

背景:疾病特异性诱导多能干细胞(iPSCs)是罕见病病理分析和诊断的有用工具。鉴于现有资源有限,储存这种源自疾病的多能干细胞并促进其广泛使用将是解开罕见疾病之谜的一种有希望的方法。在此,我们全面构建了来自日本指定顽固性疾病患者的iPSC,并评估了它们的性质,以丰富罕见病iPSC资源。方法:招募指定顽固性疾病患者,经患者或其监护人书面知情同意后采集血样。从获得的样品中,使用episomal方法建立iPSCs。建立的iPSCs储存在细胞库中。结果:我们从139种指定顽固性疾病的259例患者中建立了1532个iPSC克隆。iPSC的建立效率不受年龄和性别的影响。大多数iPSC克隆来源于非t和非b造血细胞。所有iPSC克隆均表达关键转录因子OCT3/4(范围0.27-1.51;平均0.79)和NANOG(范围0.15-3.03;平均1.00),相对于参考201B7 iPSC克隆。结论:这些新建立的多能干细胞对研究人员来说是很容易获得的,可以证明是罕见难治性疾病研究的有用资源。
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引用次数: 0
Jdp2 is a spatiotemporal transcriptional activator of the AhR via the Nrf2 gene battery. jp2是通过Nrf2基因电池激活AhR的时空转录激活因子。
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2023-08-18 DOI: 10.1186/s41232-023-00290-6
Kenly Wuputra, Ming-Ho Tsai, Kohsuke Kato, Chia-Chen Ku, Jia-Bin Pan, Ya-Han Yang, Shigeo Saito, Chun-Chieh Wu, Ying-Chu Lin, Kuang-Hung Cheng, Kung-Kai Kuo, Michiya Noguchi, Yukio Nakamura, Tohru Yoshioka, Deng-Chyang Wu, Chang-Shen Lin, Kazunari K Yokoyama

Background: Crosstalk between the aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling is called the "AhR-Nrf2 gene battery", which works synergistically in detoxification to support cell survival. Nrf2-dependent phase II gene promoters are controlled by coordinated recruitment of the AhR to adjacent dioxin responsive element (DRE) and Nrf2 recruitment to the antioxidative response element (ARE). The molecular interaction between AhR and Nrf2 members, and the regulation of each target, including phase I and II gene complexes, and their mediators are poorly understood.

Methods: Knockdown and forced expression of AhR-Nrf2 battery members were used to examine the molecular interactions between the AhR-Nrf2 axis and AhR promoter activation. Sequential immunoprecipitation, chromatin immunoprecipitation, and histology were used to identify each protein complex recruited to their respective cis-elements in the AhR promoter. Actin fiber distribution, cell spreading, and invasion were examined to identify functional differences in the AhR-Jdp2 axis between wild-type and Jdp2 knockout cells. The possible tumorigenic role of Jdp2 in the AhR-Nrf2 axis was examined in mutant Kras-Trp53-driven pancreatic tumors.

Results: Crosstalk between AhR and Nrf2 was evident at the transcriptional level. The AhR promoter was activated by phase I ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the AhR-Jdp2-Nrf2 axis in a time- and spatial transcription-dependent manner. Jdp2 was a bifunctional activator of DRE- and ARE-mediated transcription in response to TCDD. After TCDD exposure, Jdp2 activated the AhR promoter at the DRE and then moved to the ARE where it activated the promoter to increase reactive oxygen species (ROS)-mediated functions such as cell spreading and invasion in normal cells, and cancer regression in mutant Kras-Trp53-driven pancreatic tumor cells.

Conclusions: Jdp2 plays a critical role in AhR promoter activation through the AhR-Jdp2-Nrf2 axis in a spatiotemporal manner. The AhR functions to maintain ROS balance and cell spreading, invasion, and cancer regression in a mouse model of mutant Kras-Trp53 pancreatic cancer. These findings provide new insights into the roles of Jdp2 in the homeostatic regulation of oxidative stress and in the antioxidation response in detoxification, inflammation, and cancer progression.

背景:芳烃受体(AhR)和核因子(红细胞衍生2)样2 (Nrf2)信号传导之间的串扰被称为“AhR-Nrf2基因电池”,它们协同作用于解毒以支持细胞存活。Nrf2依赖的II期基因启动子通过AhR对相邻二恶英反应元件(DRE)和Nrf2对抗氧化反应元件(are)的协同募集来控制。AhR和Nrf2成员之间的分子相互作用,以及包括I期和II期基因复合物在内的每个靶标及其介质的调控尚不清楚。方法:采用敲低AhR- nrf2组成员和强制表达AhR- nrf2组成员的方法,研究AhR- nrf2轴与AhR启动子激活之间的分子相互作用。顺序免疫沉淀,染色质免疫沉淀和组织学被用来鉴定每个蛋白复合物募集到各自的顺式元件在AhR启动子。我们检测了肌动蛋白纤维分布、细胞扩散和侵袭,以确定野生型和Jdp2敲除细胞之间AhR-Jdp2轴的功能差异。在kras - trp53驱动的突变型胰腺肿瘤中,研究了Jdp2在AhR-Nrf2轴上可能的致瘤作用。结果:在转录水平上,AhR和Nrf2之间存在明显的串扰。AhR启动子被2,3,7,8-四氯二苯并-对二恶英(TCDD)等I相配体通过AhR- jdp2 - nrf2轴以时间和空间转录依赖的方式激活。Jdp2是DRE-和are -介导的转录的双功能激活剂。暴露于TCDD后,Jdp2在DRE激活AhR启动子,然后移动到ARE,激活启动子以增加活性氧(ROS)介导的功能,如正常细胞中的细胞扩散和侵袭,以及突变的kras - trp53驱动的胰腺肿瘤细胞的癌症消退。结论:Jdp2通过AhR-Jdp2- nrf2轴在AhR启动子激活中起着重要的时空作用。在Kras-Trp53突变型胰腺癌小鼠模型中,AhR发挥维持ROS平衡、细胞扩散、侵袭和癌症消退的作用。这些发现为jp2在氧化应激的稳态调节和解毒、炎症和癌症进展中的抗氧化反应中的作用提供了新的见解。
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引用次数: 0
A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo. Sox17下游基因Rasip1参与妊娠中期小鼠胚胎主动脉内造血簇的造血活性。
IF 8.1 3区 医学 Q1 Medicine Pub Date : 2023-08-08 DOI: 10.1186/s41232-023-00292-4
Gerel Melig, Ikuo Nobuhisa, Kiyoka Saito, Ryota Tsukahara, Ayumi Itabashi, Yoshiakira Kanai, Masami Kanai-Azuma, Mitsujiro Osawa, Motohiko Oshima, Atsushi Iwama, Tetsuya Taga

Background: During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta's intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45lowc-Kithigh cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity.

Methods: RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells.

Results: The increase of the Rasip1 expression level was observed in Sox17-positive CD45lowc-Kithigh cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit+Sox17+ cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45lowc-Kithigh cells led to a significant but transient increase in hematopoietic activity.

Conclusions: Rasip1 knockdown in Sox17-transduced CD45lowc-Kithigh cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithigh cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained

背景:在小鼠胚胎发育过程中,在胚胎日(E) 10.5左右,在主动脉-性腺-中肾(AGM)区域首次检测到决定性造血。造血干细胞(hsc)产生于主动脉背侧的主动脉内造血细胞簇(IAHCs)。我们之前报道过一种转录因子Sox17在IAHCs中表达,其中CD45lowc-Kithigh细胞具有较高的造血活性。此外,在这种细胞群中强制表达Sox17可以维持造血细胞簇的形成。然而,Sox17是如何做到这一点的,特别是涉及的下游信号,仍然知之甚少。本研究的目的是寻找新的Sox17靶点,这些靶点有助于形成具有造血活性的簇。方法:通过rna测序(RNA-seq)分析,鉴定表达sox17的IAHCs中与sox17阴性的IAHCs中表达上调的基因。在前7位高表达基因中,本研究重点研究了已报道的血管特异性调控基因Rasip1,首先进行了全挂载免疫染色。我们通过荧光素酶报告基因实验和染色质免疫沉淀(ChIP)实验来检测Sox17是否通过结合其增强子元件来调节Rasip1基因的表达。我们还分析了rasip1转导细胞和rasip1敲低sox17转导细胞的簇形成和多系集落形成能力。结果:与未表达sox17的对照组相比,sox17阳性CD45lowc-Kithigh细胞中Rasip1表达水平升高。此外,sox17核易位增加了Rasip1基因的表达水平。Rasip1在IAHCs的膜上表达,与内皮细胞标志物CD31和造血干细胞/祖细胞标志物c-Kit重叠。在IAHCs中,大部分c-Kit+Sox17+细胞均有Rasip1表达。荧光素酶报告基因实验和ChIP实验表明,在Rasip1增强子区域的五个推测的Sox17结合位点中,有一个对通过Sox17结合表达Rasip1很重要。在sox17转导的细胞中,Rasip1的敲低降低了簇的形成,降低了集落的形成能力,而在CD45lowc-Kithigh细胞中,Rasip1的过表达导致造血活性显著但短暂的增加。结论:在sox17转导的CD45lowc-Kithigh细胞中,Rasip1敲低显示出多系集落形成能力和簇大小的显著降低。在sox17未转导的CD45lowc-Kithigh细胞中,Rasip1过表达导致多系集落形成能力显著但短暂的增加,这表明存在一种持续造血活性的协同因子。
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Inflammation and Regeneration
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