Genes to Cells最新文献

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Paralog-Dependent Specialization of Paf1C Subunit, Ctr9, for Sex Chromosome Gene Regulation and Male Germline Differentiation in Drosophila 果蝇性染色体基因调控和雄性生殖系分化中Paf1C亚基Ctr9的同源依赖特化
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-08-05 DOI: 10.1111/gtc.70040
Toshie Kai, Jinglan Zheng, Taichiro Iki
{"title":"Paralog-Dependent Specialization of Paf1C Subunit, Ctr9, for Sex Chromosome Gene Regulation and Male Germline Differentiation in Drosophila","authors":"Toshie Kai,&nbsp;Jinglan Zheng,&nbsp;Taichiro Iki","doi":"10.1111/gtc.70040","DOIUrl":"https://doi.org/10.1111/gtc.70040","url":null,"abstract":"<p>Testis-specific gene regulatory mechanisms govern the differentiation of germ cells into mature sperm. However, the molecular underpinnings are not fully elucidated. Here, we show the subunits forming Paf1C, a transcription regulator complex conserved across eukaryotes, have their individual paralogs predominantly expressed in <i>Drosophila</i> testes. One of these, namely, Ctr9 paralog enriched in testes (Ctr9t) was found to play a critical and nonredundant role in postmeiotic spermatid differentiation and male fertility in <i>D. melanogaster</i>. A proximity proteome analysis provides evidence that Ctr9t prefers the interaction between paralog members. We show endogenous Ctr9t is expressed and functional in germ cells at spermatocyte stages, accumulating in a distinct compartment within the nucleolus. There, Ctr9t co-localizes with Spermatocyte arrest (Sa), a testis-specific paralog of TATA-binding protein (TBP)-associated factor 8 (TAF8). We further demonstrate that <i>ctr9t</i> function is crucial for maintaining Sa in the nucleolus, but not vice versa. Transcriptome profiling reveals that Ctr9t acts as an activator for the set of male fertility genes on the Y chromosome, but it also acts as a global repressor of X chromosome genes. Collectively, our results shed light on the nucleolus-associated, paralog-dependent regulation of gene expression from sex chromosomes, which ensures the terminal differentiation of male germ cells.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 5","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
TOB Proteins Repress Translation via the CCR4–NOT Deadenylase Complex Independent of Deadenylation TOB蛋白通过独立于去烯化的CCR4-NOT去烯化酶复合物抑制翻译
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-08-04 DOI: 10.1111/gtc.70042
Kanae Miyazaki, Takumi Tomohiro, Yoshinori Funakami, Akira Fukao, Toru Suzuki, Tadashi Yamamoto, Toshinobu Fujiwara
{"title":"TOB Proteins Repress Translation via the CCR4–NOT Deadenylase Complex Independent of Deadenylation","authors":"Kanae Miyazaki,&nbsp;Takumi Tomohiro,&nbsp;Yoshinori Funakami,&nbsp;Akira Fukao,&nbsp;Toru Suzuki,&nbsp;Tadashi Yamamoto,&nbsp;Toshinobu Fujiwara","doi":"10.1111/gtc.70042","DOIUrl":"https://doi.org/10.1111/gtc.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Transducer of ErbB2 (TOB) proteins have been shown to promote mRNA decay through interactions with the CCR4–NOT complex and poly(A)-binding protein (PABP). While their role in deadenylation-mediated mRNA degradation is well established, their potential function in translational control remains to be elucidated. Here, we employed an in vitro translation system combined with an RNA tethering strategy to examine the function of TOB1 and TOB2 in translation. Our results demonstrate that TOB1 and TOB2 act as repressors of translation initiation, independent of deadenylation. Notably, this translational repression selectively targets eIF4A-dependent translation, while translation driven by eIF4A-independent IRES elements remains unaffected. While the interaction between TOB proteins and PABP appears to be dispensable, as disruption of this interaction only partially reduces translational repression, the knockdown of CNOT1, the scaffold of the CCR4–NOT complex, substantially relieves this repression, highlighting its indispensable role in the mechanism. Collectively, our findings uncover a previously unrecognized function of TOB proteins as direct repressors of translation initiation, independent of mRNA decay, and highlight a specific reliance on eIF4A activity and CCR4–NOT complex integrity.</p>\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 5","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Meeting Report on the 1st Asia & Pacific Bioinformatics Joint Conference (APBJC 2024) 第一届亚太生物信息学联席会议(APBJC 2024)会议报告
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-07-03 DOI: 10.1111/gtc.70038
Kiyoko F. Aoki-Kinoshita, Susumu Goto
{"title":"Meeting Report on the 1st Asia & Pacific Bioinformatics Joint Conference (APBJC 2024)","authors":"Kiyoko F. Aoki-Kinoshita,&nbsp;Susumu Goto","doi":"10.1111/gtc.70038","DOIUrl":"https://doi.org/10.1111/gtc.70038","url":null,"abstract":"<p>The 1st Asia &amp; Pacific Bioinformatics Conference (APBJC) covers a wide range of scientific topics in the oral sessions (black) and workshops (red) as well as the poster session. The numbers in parentheses indicate the number of presentations in each session. AI-related topics were found to be connected to many of the session themes.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Effect of Retinal on Dictyostelium Cells During Development 视网膜对盘状骨细胞发育的影响
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-07-02 DOI: 10.1111/gtc.70037
Kazuki Akiyama, Shuhei Tsuchihashi, Yusuke V. Morimoto
{"title":"Effect of Retinal on Dictyostelium Cells During Development","authors":"Kazuki Akiyama,&nbsp;Shuhei Tsuchihashi,&nbsp;Yusuke V. Morimoto","doi":"10.1111/gtc.70037","DOIUrl":"https://doi.org/10.1111/gtc.70037","url":null,"abstract":"<p>Retinal plays a key role in light absorption across prokaryotes and eukaryotes, both in rhodopsin and bacteriorhodopsin systems. The multicellular social amoeba <i>Dictyostelium discoideum</i> exhibits positive phototaxis. However, retinal binding proteins such as rhodopsin have not been found in the genome of <i>Dictyostelium</i> cells. Herein, we microscopically examined the effects of retinal on <i>Dictyostelium</i> cells. On adding all-<i>trans</i>-retinal to the medium, <i>Dictyostelium</i> cells retracted their pseudopodia and became rounded. This was unique to retinal among the tested vitamin A variants. Addition of all-<i>trans</i>-retinal at low concentrations did not cause cell rounding. However, it increased the frequency of cAMP signaling triggered during cell development. Results indicate that retinal acts on an unknown signaling pathway involving the cytoskeleton in <i>Dictyostelium</i> cells.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Effects of VEGFA and ANGPT2 Antibodies on the Activation of Microglia in the Early Stages of Streptozotocin-Induced Pathogenesis of Diabetic Retinopathy vegf和ANGPT2抗体对链脲佐菌素诱导的糖尿病视网膜病变早期小胶质细胞活化的影响
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-24 DOI: 10.1111/gtc.70036
Toshiro Iwagawa, Yuta Inokuchi, Kosuke Saita, Tetsuhiro Soeda, Ayumi Usui-Ouchi, Makoto Aihara, Sumiko Watanabe
{"title":"Effects of VEGFA and ANGPT2 Antibodies on the Activation of Microglia in the Early Stages of Streptozotocin-Induced Pathogenesis of Diabetic Retinopathy","authors":"Toshiro Iwagawa,&nbsp;Yuta Inokuchi,&nbsp;Kosuke Saita,&nbsp;Tetsuhiro Soeda,&nbsp;Ayumi Usui-Ouchi,&nbsp;Makoto Aihara,&nbsp;Sumiko Watanabe","doi":"10.1111/gtc.70036","DOIUrl":"https://doi.org/10.1111/gtc.70036","url":null,"abstract":"<p>Diabetic retinopathy (DR) is known as a microvascular complication, in which various inflammatory symptoms, including activation of microglia, are observed. A model of hyperglycemia resembling type 1 diabetes mellitus (DM) induced in mice by intraperitoneal injection of streptozotocin (STZ) has been widely used. We examined the effects of anti- vascular endothelial growth factor A (VEGFA) and anti-angiopoietin-2 (ANGPT2) antibodies in addition to a bispecific antibody against VEGFA and ANGPT2 by intravitreously administrated to the eyes on early signs, especially the activation of microglia in STZ-treated mice eyes. After 14 weeks of STZ administration, alterations in activity by ERG and CD31 staining patterns were not observed. Although a difference in the number of microglia in the retina between normal and STZ-model retinas was not observed, the morphology of microglia had changed from ramified in control to amoeboid shape in STZ model at 4 days after the antibodies injection. Detailed morphological examination showed decreases in area, ramification index, and tree length in the STZ-model retinas compared with normal retinas. Recovery from these decreases was demonstrated mainly by the administration of the bispecific antibody. These results suggest that anti-VEGFA/ANGPT2 therapy may suppress the activation of microglia in the early stages of DR.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Effects of Dual Inhibition of VEGF-A and Angpt-2 on Angiogenesis and Lymphangiogenesis in an Alkali-Induced Corneal Injury Model VEGF-A和Angpt-2双重抑制对碱性角膜损伤模型血管生成和淋巴管生成的影响
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-24 DOI: 10.1111/gtc.70035
Hiroshi Kuribayashi, Toshiro Iwagawa, Souta Kadohara, Hirokazu Ohashi, Chihiro Kawaji, Takeru Iida, Tomoya Suzuki, Yuta Inokuchi, Tetsuhiro Soeda, Kosuke Saita, Makoto Aihara, Nobuyuki Ebihara, Takashi Miyai, Sumiko Watanabe
{"title":"Effects of Dual Inhibition of VEGF-A and Angpt-2 on Angiogenesis and Lymphangiogenesis in an Alkali-Induced Corneal Injury Model","authors":"Hiroshi Kuribayashi,&nbsp;Toshiro Iwagawa,&nbsp;Souta Kadohara,&nbsp;Hirokazu Ohashi,&nbsp;Chihiro Kawaji,&nbsp;Takeru Iida,&nbsp;Tomoya Suzuki,&nbsp;Yuta Inokuchi,&nbsp;Tetsuhiro Soeda,&nbsp;Kosuke Saita,&nbsp;Makoto Aihara,&nbsp;Nobuyuki Ebihara,&nbsp;Takashi Miyai,&nbsp;Sumiko Watanabe","doi":"10.1111/gtc.70035","DOIUrl":"https://doi.org/10.1111/gtc.70035","url":null,"abstract":"<p>Corneal neovascularization (CNV) is frequently observed after various corneal injuries and corneal transplantation, leading to impairment of corneal transparency. Lymphangiogenesis and the inflammatory response often accompany CNV. Chemical injury is one of the most common causes of CNV, and alkali injury has been widely used as an animal model of this pathological state. We examined the effects of subconjunctival injection of an anti-VEGFA antibody (anti-VEGFA_ab), anti-ANGPT2 antibody (anti-ANGPT2_ab), and bispecific antibody against VEGFA and ANGPT2 (BsAb) in CNV using the alkali injury mouse model. The pathological indexes were examined using anterior segment optical coherence tomography (OCT) and whole-mount immunostaining, and gene expression patterns were examined using RT-qPCR. Treatment with anti-VEGFA_ab, anti-ANGPT2_ab, or BsAb did not affect the swelled thickness of the cornea; however, angiogenesis, but not lymphangiogenesis, was hampered by the treatment of either one of the antibodies. We observed an increase in the mRNA levels of <i>Vegfa</i>, <i>Angpt2</i>, <i>Il1b</i>, and <i>Cx3cr1</i> following alkali injury. The administration of BsAb suppressed the induction of <i>Vegfa</i> and <i>Cx3cr1</i>. Additionally, BsAb treatment enhanced the mRNA levels of <i>Angpt1</i> in this model. This study demonstrates the potential of dual VEGFA and ANGPT2 inhibition as a therapeutic strategy for CNV.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Functional Analysis of Adhesion GPCR Latrophilin 2 (ADGRL2) in MDA-MB-231 Human Breast Cancer Cells MDA-MB-231人乳腺癌细胞粘附GPCR亲Latrophilin 2 (ADGRL2)的功能分析
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-22 DOI: 10.1111/gtc.70030
Sarmoko, Manami Toriyama, Noriko Kaji, Hiroshi Itoh
{"title":"Functional Analysis of Adhesion GPCR Latrophilin 2 (ADGRL2) in MDA-MB-231 Human Breast Cancer Cells","authors":"Sarmoko,&nbsp;Manami Toriyama,&nbsp;Noriko Kaji,&nbsp;Hiroshi Itoh","doi":"10.1111/gtc.70030","DOIUrl":"https://doi.org/10.1111/gtc.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>The tumor microenvironment strongly influences cancer cell behavior, including growth, migration, invasiveness, and gene expression dynamics. Adhesion G protein-coupled receptors (aGPCR) play critical roles in cell–cell or cell-extracellular matrix (ECM) interaction. This study aims to investigate the functions and elucidate signaling of Latrophilin-2 (LPHN2), an aGPCR, in breast cancer progression using MDA-MB-231 cells. LPHN2-deficient MDA-MB-231 cells exhibited decreased invasion-like sphere structure in 3D culture, reduced proliferation, diminished adhesion to collagen I, and impaired migration activity. Reporter assays and pharmacological inhibition experiments revealed that the C-terminal fragment (CTF) of LPHN2 activates SRE- and CREB-mediated gene transcription while activating ROCK and PKA signaling pathways. Additionally, downregulation of Gα12/13 and Gαs reduced cell migration in both wild-type and CTF-overexpressing LPHN2-knockout cells, demonstrating that LPHN2 couples to Gα12/13 and Gαs signaling pathways. These findings highlight the functional significance of LPHN2 in breast cancer cell behavior and provide potential therapeutic targets for breast cancer intervention.</p>\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Long Noncoding RNA CCDC26 Interacts With Vimentin, HNRNPC, CBX1, and CBX5 Proteins in Multiple Intracellular Compartments of Myeloid Leukemia Cells 长链非编码RNA CCDC26在髓系白血病细胞内多个区室中与Vimentin、HNRNPC、CBX1和CBX5蛋白相互作用
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-15 DOI: 10.1111/gtc.70034
Yuka Tanaka, Atsuhiko Ishida, Hironori Harada, Tetsuo Hirano
{"title":"Long Noncoding RNA CCDC26 Interacts With Vimentin, HNRNPC, CBX1, and CBX5 Proteins in Multiple Intracellular Compartments of Myeloid Leukemia Cells","authors":"Yuka Tanaka,&nbsp;Atsuhiko Ishida,&nbsp;Hironori Harada,&nbsp;Tetsuo Hirano","doi":"10.1111/gtc.70034","DOIUrl":"https://doi.org/10.1111/gtc.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Long noncoding RNAs (lncRNAs) are involved in various biological events. Previously we reported that lncRNA CCDC26 controls myeloid leukemia cell proliferation and mortality by regulating the proto-oncogene KIT. However, the mechanism of lncRNA CCDC26 effects on carcinogenesis and cell differentiation remains unclarified. To investigate the mechanism of lncRNA CCDC26 activity, we analyzed its protein partners using the S1 aptamer/cross-linking-immunoprecipitation (S1-CLIP) experiment. We identified a cytoskeleton protein (vimentin), chromatin proteins (chromobox 1/5 transcription factors [CBX1 and CBX5]) and a nuclear splicing-related protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) as its interaction partners. As lncRNA CCDC26 is ubiquitously present in the cell (in cytoplasm, nucleoplasm, and chromatin cellular fractions); these results evidence that lncRNA CCDC26 is a unique multifunctional lncRNA that functions by interacting with several proteins in multiple intracellular compartments. We further identified the sequence through which it interacts with proteins by using a series of truncated-lncRNA CCDC26 fragments and RNA immunoprecipitation (RIP) experiments. Furthermore, using RIP, we identified the vimentin domain required for the lncRNA CCDC26 binding. Notably, CCDC26 knockdown reduced CBX1/CBX5 binding at certain gene promoters, correlating with increased gene expression. These findings suggest that CCDC26 may regulate transcription by interacting with CBX1 and CBX5.</p>\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
RNF213-Dependent EGFR and HER2 Activation Regulates Specific Downstream Signaling Pathways in Human Cancer Cells 依赖rnf213的EGFR和HER2激活调节人类癌细胞特异性下游信号通路
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-12 DOI: 10.1111/gtc.70033
Intisar M. Fouad, Jungmi Choi, Qianying Huang, Minsoo Kim, Seiji Masuda, James A. Hejna, Yohei Mineharu, Akio Koizumi, Tohru Tezuka, Shohab Youssefian
{"title":"RNF213-Dependent EGFR and HER2 Activation Regulates Specific Downstream Signaling Pathways in Human Cancer Cells","authors":"Intisar M. Fouad,&nbsp;Jungmi Choi,&nbsp;Qianying Huang,&nbsp;Minsoo Kim,&nbsp;Seiji Masuda,&nbsp;James A. Hejna,&nbsp;Yohei Mineharu,&nbsp;Akio Koizumi,&nbsp;Tohru Tezuka,&nbsp;Shohab Youssefian","doi":"10.1111/gtc.70033","DOIUrl":"https://doi.org/10.1111/gtc.70033","url":null,"abstract":"<p>In this study, we reveal a novel relationship between RNF213, an E3 ubiquitin ligase associated with Moyamoya disease (MMD) and the ubiquitination of both endogenous and pathogenic substrates, and EGFR, the epithelial growth factor receptor involved in cell growth, angiogenesis, and cancer. RNF213 knockdown or knockout in HeLa and A549 cells markedly reduces EGFR phosphorylation at key tyrosine sites following EGF and TGFα stimulation. In RNF213 knockout cells, HER2 phosphorylation, typically activated through heterodimerization with EGFR, and Src recruitment and/or phosphorylation are also diminished. Mutations in the RNF213 RING, RZ finger, or AAA+ domains, including the prevalent R4810K mutation in MMD, consistently reduce EGFR phosphorylation. In vivo, EGF injections increase EGFR and HER2 phosphorylation in WT but not in RNF213 knockout mice. Despite the reduced phosphorylation levels of these tyrosine kinases in knockout cells, the activation of downstream signals such as AKT, ERK1/2, and STAT3 remains unaffected, although phosphorylation of PLCγ, a key mediator of Ca<sup>2+</sup> release, is selectively reduced by RNF213 knockout. These findings demonstrate that RNF213 modulates EGFR-related pathways and specific downstream signal pathways, possibly affecting physiologic and pathogenic angiogenesis, and may have implications for unraveling the etiology of MMD and for developing cancer therapies that target RNF213.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Microenvironment-Dependent MSC Immunoregulation in Type 1 Diabetes: Insights From IFNγ Preconditioning 1型糖尿病中依赖微环境的MSC免疫调节:来自IFNγ预处理的见解
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2025-06-10 DOI: 10.1111/gtc.70032
Seyed Mehdi Hoseini, Farnoosh Moghimi, Elham Sadat Hosseini, Seyed Mohsen Miresmaeili, Mohammad Yahya Vahidi Mehrjardi, Mohammadreza Dehghani, Mohammad Hasan Sheikhha, Fateme Montazeri
{"title":"Microenvironment-Dependent MSC Immunoregulation in Type 1 Diabetes: Insights From IFNγ Preconditioning","authors":"Seyed Mehdi Hoseini,&nbsp;Farnoosh Moghimi,&nbsp;Elham Sadat Hosseini,&nbsp;Seyed Mohsen Miresmaeili,&nbsp;Mohammad Yahya Vahidi Mehrjardi,&nbsp;Mohammadreza Dehghani,&nbsp;Mohammad Hasan Sheikhha,&nbsp;Fateme Montazeri","doi":"10.1111/gtc.70032","DOIUrl":"https://doi.org/10.1111/gtc.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Interferon-gamma (IFNγ) plays a crucial role in the pathogenesis of type 1 diabetes (T1D) and is widely utilized to license mesenchymal stem/stromal cells (MSCs) to enhance their immunosuppressive properties through a process known as preconditioning or priming. This study investigates the interaction of MSCs preconditioned with (IFNγ<sup>+</sup>) or without (IFNγ<sup>−</sup>) IFNγ, with peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) and T1D patients. We assessed the effects of these interactions on anti-inflammatory gene expression, chemokine and receptor profiles, and the induction of regulatory T (Treg) cells. Our findings reveal contrasting responses in HC and T1D PBMCs when exposed to IFNγ<sup>+</sup> and IFNγ<sup>−</sup> MSCs, particularly in the expression of key genes such as <i>CXCR3</i> and its ligands (<i>CXCL9</i>, <i>CXCL10</i>), <i>CXCR6</i>, <i>CCR5</i>, and its ligands (<i>CCL3</i> and <i>CCL4</i>). Pathway enrichment analysis further showed that IFNγ preconditioning tailors MSC responses to specific immune microenvironments. These differential gene expression patterns were also reflected in the proportions of Treg cells, which varied depending on whether paracrine signaling or direct cell contact was involved. Collectively, our results demonstrate that IFNγ<sup>+</sup> and IFNγ<sup>−</sup> MSCs create distinct immunomodulatory microenvironments in T1D PBMCs compared to HC PBMCs, emphasizing the potential for tailored MSC-based therapies in T1D treatment.</p>\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 4","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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