المؤلفون: Bankell, Elisabeth, Liu, Li, van der Horst, Jennifer, Rippe, Catarina, Jepps, Thomas A, Nilsson, Bengt-Olof, Swärd, Karl

المصدر: Scientific Reports. 14(1)

مصطلحات موضوعية: Humans, Protein Serine-Threonine Kinases/metabolism, Nuclear Proteins/metabolism, Myocytes, Smooth Muscle/metabolism, Trans-Activators/metabolism, Inflammation/metabolism, Signal Transduction, Cytokines/metabolism, Phosphorylation, Transcription Factors/metabolism, Membrane Proteins/metabolism, Cells, Cultured, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Cell- och molekylärbiologi, Medical and Health Sciences, Basic Medicine, Cell and Molecular Biology, Immunologi inom det medicinska området, Immunology in the medical area

الوصف: Myocardin-related transcription factors (MRTFs: myocardin/MYOCD, MRTF-A/MRTFA, and MRTF-B/MRTFB) suppress production of pro-inflammatory cytokines and chemokines in human smooth muscle cells (SMCs) through sequestration of RelA in the NF-κB complex, but additional mechanisms are likely involved. The cGAS-STING pathway is activated by double-stranded DNA in the cytosolic compartment and acts through TANK-binding kinase 1 (TBK1) to spark inflammation. The present study tested if MRTFs suppress inflammation also by targeting cGAS-STING signaling. Interrogation of a transcriptomic dataset where myocardin was overexpressed using a panel of 56 cGAS-STING cytokines showed the panel to be repressed. Moreover, MYOCD, MRTFA, and SRF associated negatively with the panel in human arteries. RT-qPCR in human bronchial SMCs showed that all MRTFs reduced pro-inflammatory cytokines on the panel. MRTFs diminished phosphorylation of TBK1, while STING phosphorylation was marginally affected. The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A. Co-immunoprecipitation and proximity ligation assays supported binding between MRTF-A and TBK1 in SMCs. MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease.

الوصول الحر: https://lup.lub.lu.se/record/a35b24ab-34ab-482b-a56b-1f62877f6db7Test
http://dx.doi.org/10.1038/s41598-024-63901-3Test

المؤلفون: Trovato, Francesco, Stefani, Francesca Romana, Li, Jiaxin, Zetterdahl, Oskar G, Canals, Isaac, Ahlenius, Henrik, Bengzon, Johan

المصدر: Molecular Cancer Therapeutics MultiPark: Multidisciplinary research focused on Parkinson´s disease StemTherapy: National Initiative on Stem Cells for Regenerative Therapy. 22(2):274-286

مصطلحات موضوعية: Humans, Glioblastoma/drug therapy, Astrocytes, Transcription Factors/metabolism, Brain Neoplasms/drug therapy, Cell Line, Tumor, Cell Differentiation, Neoplastic Stem Cells/metabolism, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Cell- och molekylärbiologi, Medical and Health Sciences, Basic Medicine, Cell and Molecular Biology

الوصف: Direct cellular reprogramming has recently gained attention of cancer researchers for the possibility to convert undifferentiated cancer cells into more differentiated, postmitotic cell types. While a few studies have attempted reprogramming of glioblastoma (GBM) cells toward a neuronal fate, this approach has not yet been used to induce differentiation into other lineages and in vivo data on reduction in tumorigenicity are limited. Here, we employ cellular reprogramming to induce astrocytic differentiation as a therapeutic approach in GBM. To this end, we overexpressed key transcriptional regulators of astroglial development in human GBM and GBM stem cell lines. Treated cells undergo a remarkable shift in structure, acquiring an astrocyte-like morphology with star-shaped bodies and radial branched processes. Differentiated cells express typical glial markers and show a marked decrease in their proliferative state. In addition, forced differentiation induces astrocytic functions such as induced calcium transients and ability to respond to inflammatory stimuli. Most importantly, forced differentiation substantially reduces tumorigenicity of GBM cells in an in vivo xenotransplantation model. The current study capitalizes on cellular plasticity with a novel application in cancer. We take advantage of the similarity between neural developmental processes and cancer hierarchy to mitigate, if not completely abolish, the malignant nature of tumor cells and pave the way for new intervention strategies.

الوصول الحر: https://lup.lub.lu.se/record/7676bba6-688b-4078-9f4a-8a4493e6bd4dTest
http://dx.doi.org/10.1158/1535-7163.MCT-21-0903Test

المؤلفون: Han, Han, Nakaoka, Hiroki J, Hofmann, Line, Zhou, Jeff Jiajing, Yu, Clinton, Zeng, Lisha, Nan, Junyu, Seo, Gayoung, Vargas, Rebecca Elizabeth, Yang, Bing, Qi, Ruxi, Bardwell, Lee, Fishman, Dmitry A, Cho, Ken W Y, Huang, Lan, Luo, Ray, Warrior, Rahul, Wang, Wenqi

المصدر: Nature cell biology. 24(1)

مصطلحات موضوعية: Cadmium: metabolism, toxicity, Cell Line, Tumor, DNA-Binding Proteins: metabolism, Gene Expression Regulation: genetics, HEK293 Cells, HeLa Cells, Hippo Signaling Pathway: physiology, Homeostasis: genetics, Humans, Inactivation, Metabolic: physiology, Phosphorylation, Protein Serine-Threonine Kinases: genetics, metabolism, Stress, Physiological: physiology, Transcription Factors: metabolism, Transcription, Genetic: genetics, Tumor Suppressor Proteins: genetics, metabolism, Zinc: metabolism, toxicity

الوصف: Heavy metals are both integral parts of cells and environmental toxicants, and their deregulation is associated with severe cellular dysfunction and various diseases. Here we show that the Hippo pathway plays a critical role in regulating heavy metal homeostasis. Hippo signalling deficiency promotes the transcription of heavy metal response genes and protects cells from heavy metal-induced toxicity, a process independent of its classic downstream effectors YAP and TAZ. Mechanistically, the Hippo pathway kinase LATS phosphorylates and inhibits MTF1, an essential transcription factor in the heavy metal response, resulting in the loss of heavy metal response gene transcription and cellular protection. Moreover, LATS activity is inhibited following heavy metal treatment, where accumulated zinc directly binds and inhibits LATS. Together, our study reveals an interplay between the Hippo pathway and heavy metals, providing insights into this growth-related pathway in tissue homeostasis and stress response.

الوصول الحر: https://escholarship.org/uc/item/86g8n13nTest

المؤلفون: Baßler, Kevin, Schmidleithner, Lisa, Neubauer, Anna, Sakaguchi, Shimon, Barry, Simon C, Huehn, Jochen, Bonaguro, Lorenzo, Ulas, Thomas, Beyer, Marc-Daniel, Hadaddzadeh Shakiba, Mehrnoush, Elmzzahi, Tarek, Köhne, Maren, Floess, Stefan, Scholz, Rebekka, Ohkura, Naganari, Sadlon, Timothy, Klee, Kathrin

المصدر: Frontiers in immunology 14, 1107397 (2023). doi:10.3389/fimmu.2023.1107397

مصطلحات موضوعية: info:eu-repo/classification/ddc/610, Humans, T-Lymphocytes, Regulatory, Gene Expression Regulation, Gene Regulatory Networks, Forkhead Transcription Factors: genetics, Forkhead Transcription Factors: metabolism, Transcription Factors: metabolism, Homeodomain Proteins: genetics, Forkhead Transcription Factors, Foxp3, MEOX1, Treg cells, human CD4, regulatory T cells, FOXP3 protein, human, MEOX1 protein, Transcription Factors, Homeodomain Proteins

جغرافية الموضوع: DE

الوصف: CD4+ T cells play a central role in the adaptive immune response through their capacity to activate, support and control other immune cells. Although these cells have become the focus of intense research, a comprehensive understanding of the underlying regulatory networks that orchestrate CD4+ T cell function and activation is still incomplete. Here, we analyzed a large transcriptomic dataset consisting of 48 different human CD4+ T cell conditions. By performing reverse network engineering, we identified six common denominators of CD4+ T cell functionality (CREB1, E2F3, AHR, STAT1, NFAT5 and NFATC3). Moreover, we also analyzed condition-specific genes which led us to the identification of the transcription factor MEOX1 in Treg cells. Expression of MEOX1 was comparable to FOXP3 in Treg cells and can be upregulated by IL-2. Epigenetic analyses revealed a permissive epigenetic landscape for MEOX1 solely in Treg cells. Knockdown of MEOX1 in Treg cells revealed a profound impact on downstream gene expression programs and Treg cell suppressive capacity. These findings in the context of CD4+ T cells contribute to a better understanding of the transcriptional networks and biological mechanisms controlling CD4+ T cell functionality, which opens new avenues for future therapeutic strategies.

العلاقة: info:eu-repo/semantics/altIdentifier/issn/1664-3224; info:eu-repo/semantics/altIdentifier/pmid/pmid:37559728; https://pub.dzne.de/record/259713Test; https://pub.dzne.de/search?p=id:%22DZNE-2023-00785%22Test

الإتاحة: https://doi.org/10.3389/fimmu.2023.1107397Test
https://pub.dzne.de/record/259713Test
https://pub.dzne.de/search?p=id:%22DZNE-2023-00785%22Test

المؤلفون: Akol, Ipek, Izzo, Annalisa, Fischer, Andre, Manke, Thomas, Vogel, Tanja, Gather, Fabian, Strack, Stefanie, Heidrich, Stefanie, Ó hAilín, Darren, Villarreal, Alejandro, Hacker, Christine, Rauleac, Tudor, Bella, Chiara

المصدر: Proceedings of the National Academy of Sciences of the United States of America 120(2), e2122467120 (2023). doi:10.1073/pnas.2122467120

مصطلحات موضوعية: info:eu-repo/classification/ddc/500, Mice, Animals, Forkhead Transcription Factors: genetics, Forkhead Transcription Factors: metabolism, Rett Syndrome: genetics, Epigenesis, Genetic, Chromatin: genetics, Chromatin: metabolism, Hippocampus: metabolism, Nerve Tissue Proteins: genetics, Nerve Tissue Proteins: metabolism, Basic Helix-Loop-Helix Transcription Factors: genetics, Basic Helix-Loop-Helix Transcription Factors: metabolism, ATAC, Rett-syndrome, axonogenesis, histone modification, neuronal differentiation, Forkhead Transcription Factors, Chromatin, Foxg1 protein, mouse, Nerve Tissue Proteins, Neurod1 protein, Basic Helix-Loop-Helix Transcription Factors

جغرافية الموضوع: DE

الوصف: Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction.

العلاقة: info:eu-repo/semantics/altIdentifier/issn/0027-8424; info:eu-repo/semantics/altIdentifier/pmid/pmid:36598943; info:eu-repo/semantics/altIdentifier/issn/1091-6490; https://pub.dzne.de/record/169280Test; https://pub.dzne.de/search?p=id:%22DZNE-2023-00118%22Test

الإتاحة: https://doi.org/10.1073/pnas.2122467120Test
https://pub.dzne.de/record/169280Test
https://pub.dzne.de/search?p=id:%22DZNE-2023-00118%22Test

المؤلفون: Spielmann, Julien, Schloesser, Marie, Hanikenne, Marc

المصدر: Plant, Cell and Environment, 47 (6), 2093 - 2108 (2024-06)

مصطلحات موضوعية: ZIP, hyperaccumulation, metal toxicity, metal transport, transcription factor, Arabidopsis Proteins, Basic-Leucine Zipper Transcription Factors, Cadmium, MicroRNAs, Zinc, bZIP23 protein, Arabidopsis, bZIP19 protein, Arabidopsis, MicroRNAs/metabolism, MicroRNAs/genetics, Plant Roots/metabolism, Plant Roots/genetics, Plant Shoots/metabolism, Plant Shoots/genetics, Arabidopsis/metabolism, Arabidopsis/genetics, Arabidopsis Proteins/metabolism, Arabidopsis Proteins/genetics, Basic-Leucine Zipper Transcription Factors/metabolism, Basic-Leucine Zipper Transcription Factors/genetics, Cadmium/metabolism, Gene Expression Regulation, Plant, Zinc/metabolism, Arabidopsis, Plant Roots, Plant Shoots, Physiology, Plant Science, Life sciences, Phytobiology (plant sciences, forestry, mycology...), Sciences du vivant, Biologie végétale (sciences végétales, sylviculture, mycologie...)

الوصف: Zinc is an essential micronutrient for all living organisms. When challenged by zinc-limiting conditions, Arabidopsis thaliana plants use a strategy centered on two transcription factors, bZIP19 and bZIP23, to enhance the expression of several zinc transporters to improve their zinc uptake capacity. In the zinc and cadmium hyperaccumulator plant Arabidopsis halleri, highly efficient root-to-shoot zinc translocation results in constitutive local zinc deficiency in roots and in constitutive high expression of zinc deficiency-responsive ZIP genes, supposedly boosting zinc uptake and accumulation. Here, to disrupt this process and to analyze the functions of AhbZIP19, AhbZIP23 and their target genes in hyperaccumulation, the genes encoding both transcriptional factors were knocked down using artificial microRNAs (amiRNA). Although AhbZIP19, AhbZIP23, and their ZIP target genes were downregulated, amiRNA lines surprisingly accumulated more zinc and cadmium compared to control lines in both roots and shoot driving to shoot toxicity symptoms. These observations suggested the existence of a substitute metal uptake machinery in A. halleri to maintain hyperaccumulation. We propose that the iron uptake transporter AhIRT1 participates in this alternative pathway in A. halleri.

العلاقة: https://onlinelibrary.wiley.com/doi/pdf/10.1111/pce.14862Test; urn:issn:0140-7791; urn:issn:1365-3040

الوصول الحر: https://orbi.uliege.be/handle/2268/319417Test

المؤلفون: Chohra, Ilyas, Chung, Keshi, Giri, Subhajit, Malgrange, Brigitte

المصدر: Cells, 12 (4) (2023-02-07)

مصطلحات موضوعية: Chromatin, Transcription Factors, 8L70Q75FXE (Adenosine Triphosphate), Humans, Transcription Factors/metabolism, Chromatin Assembly and Disassembly, Adenosine Triphosphate/metabolism, Hearing Loss, Sensorineural, cochlea, development, differentiation, epigenetic, hair cells, Life sciences, Biochemistry, biophysics & molecular biology, Human health sciences, Otolaryngology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire, Sciences de la santé humaine, Oto-rhino-laryngologie

الوصف: During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting enzymes. ATP-dependent chromatin remodelling complexes use the energy of ATP hydrolysis to modify chromatin architecture by repositioning and rearranging nucleosomes. These complexes are defined by a conserved SNF2-like, catalytic ATPase subunit and are divided into four families: CHD, SWI/SNF, ISWI and INO80. ATP-dependent chromatin remodellers are crucial in regulating development and stem cell biology in numerous organs, including the inner ear. In addition, mutations in genes coding for proteins that are part of chromatin remodellers have been implicated in numerous cases of neurosensory deafness. In this review, we describe the composition, structure and functional activity of these complexes and discuss how they contribute to hearing and neurosensory deafness.

العلاقة: urn:issn:2073-4409

الوصول الحر: https://orbi.uliege.be/handle/2268/300765Test

المساهمون: Dong Yun Kim, Yu Jin Sub, Hye-Youn Kim, Kyeong Jee Cho, Won Il Choi, Yo Jun Choi, Min Goo Lee, Friedhelm Hildebrandt, Heon Yung Gee, Kim, Hye-Youn

مصطلحات موضوعية: Animals, Cilia* / metabolism, Cytoskeletal Proteins / metabolism, Dyneins* / genetics, Dyneins* / metabolism, Forkhead Transcription Factors* / metabolism, Gene Expression Regulation, Mice, Knockout, Proteins / genetics, Proteomics, FOXJ1, LRRC6, Motile cilia, Nuclear translocation, Primary ciliary dyskinesia

الوصف: Background: LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription. Methods: We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings. Results: The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor. Conclusions: Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. Video Abstract ; open

العلاقة: CELL COMMUNICATION AND SIGNALING; J00480; OAK-2023-02322; OAK-2023-02323; OAK-2023-02324; https://ir.ymlib.yonsei.ac.kr/handle/22282913/195965Test; T202304162; CELL COMMUNICATION AND SIGNALING, Vol.21(1) : 142, 2023-06

الإتاحة: https://doi.org/10.1186/s12964-023-01135-yTest
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195965Test

المساهمون: Jiwon Kim, A Young Sim, Sumit Barua, Jong Youl Kim, Jong Eun Lee, Kim, Jong Youl

مصطلحات موضوعية: Agmatine* / metabolism, Agmatine* / pharmacology, Carrier Proteins / metabolism, DNA-Binding Proteins, Humans, Inflammation / metabolism, Interferon Regulatory Factor-2 / metabolism, Interferon Regulatory Factor-2 / pharmacology, Kruppel-Like Factor 4, Lipopolysaccharides / metabolism, Lipopolysaccharides / pharmacology, Microglia / metabolism, Neuroinflammatory Diseases, Phenotype, Transcription Factors / metabolism, Agmatine, IRF2, IRF2BP2, KLF4, Microglia, Neuroinflammation

الوصف: Background: Following central nervous system (CNS) injury, the investigation for neuroinflammation is vital because of its pleiotropic role in both acute injury and long-term recovery. Agmatine (Agm) is well known for its neuroprotective effects and anti-neuroinflammatory properties. However, Agm's mechanism for neuroprotection is still unclear. We screened target proteins that bind to Agm using a protein microarray; the results showed that Agm strongly binds to interferon regulatory factor 2 binding protein (IRF2BP2), which partakes in the inflammatory response. Based on these prior data, we attempted to elucidate the mechanism by which the combination of Agm and IRF2BP2 induces a neuroprotective phenotype of microglia. Methods: To confirm the relationship between Agm and IRF2BP2 in neuroinflammation, we used microglia cell-line (BV2) and treated with lipopolysaccharide from Escherichia coli 0111:B4 (LPS; 20 ng/mL, 24 h) and interleukin (IL)-4 (20 ng/mL, 24 h). Although Agm bound to IRF2BP2, it failed to enhance IRF2BP2 expression in BV2. Therefore, we shifted our focus onto interferon regulatory factor 2 (IRF2), which is a transcription factor and interacts with IRF2BP2. Results: IRF2 was highly expressed in BV2 after LPS treatment but not after IL-4 treatment. When Agm bound to IRF2BP2 following Agm treatment, the free IRF2 translocated to the nucleus of BV2. The translocated IRF2 activated the transcription of Kruppel-like factor 4 (KLF4), causing KLF4 to be induced in BV2. The expression of KLF4 increased the CD206-positive cells in BV2. Conclusions: Taken together, unbound IRF2, resulting from the competitive binding of Agm to IRF2BP2, may provide neuroprotection against neuroinflammation via an anti-inflammatory mechanism of microglia involving the expression of KLF4. ; restriction

العلاقة: INFLAMMATION RESEARCH; J01059; OAK-2023-01936; OAK-2023-01937; https://ir.ymlib.yonsei.ac.kr/handle/22282913/195502Test; https://link.springer.com/article/10.1007/s00011-023-01741-zTest; T202303395; INFLAMMATION RESEARCH, Vol.72(6) : 1203-1213, 2023-06

الإتاحة: https://doi.org/10.1007/s00011-023-01741-zTest
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195502Test

المساهمون: Hyeyeon Choi, Jong Pil Yun, Ari Lee, Sang-Sun Han, Sang Woo Kim, Chena Lee, Lee, Chena

مصطلحات موضوعية: Humans, Ischemia / etiology, Janus Kinases / metabolism, Polydeoxyribonucleotides* / therapeutic use, Reperfusion Injury* / metabolism, STAT Transcription Factors / metabolism, Signal Transduction

الوصف: Cone-beam computed tomography (CBCT) produces high-resolution of hard tissue even in small voxel size, but the process is associated with radiation exposure and poor soft tissue imaging. Thus, we synthesized a CBCT image from the magnetic resonance imaging (MRI), using deep learning and to assess its clinical accuracy. We collected patients who underwent both CBCT and MRI simultaneously in our institution (Seoul). MRI data were registered with CBCT data, and both data were prepared into 512 slices of axial, sagittal, and coronal sections. A deep learning-based synthesis model was trained and the output data were evaluated by comparing the original and synthetic CBCT (syCBCT). According to expert evaluation, syCBCT images showed better performance in terms of artifacts and noise criteria but had poor resolution compared to the original CBCT images. In syCBCT, hard tissue showed better clarity with significantly different MAE and SSIM. This study result would be a basis for replacing CBCT with non-radiation imaging that would be helpful for patients planning to undergo both MRI and CBCT. © 2023. The Author(s). ; open

العلاقة: SCIENTIFIC REPORTS; J02646; OAK-2023-01180; OAK-2023-01181; https://ir.ymlib.yonsei.ac.kr/handle/22282913/194259Test; T202302788; SCIENTIFIC REPORTS, Vol.13(1) : 6031, 2023-04

الإتاحة: https://doi.org/10.1038/s41598-023-33288-8Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/194259Test