GATA Transcription Factors Research Articles

Insight into the anti-allergic impacts of fucoidan from Gracilaria lemaneiformis in mitigating allergic reactions induced by shrimp tropomyosin via regulating Th1/Th2 cytokines and T cell subsets.

Fucoidan is a natural sulfated polysaccharide with immunoregulatory function. In this work, the anti-allergic impacts of Gracilaria lemaneiformis fucoidan (GLF) in mitigating allergic reactions induced by shrimp tropomyosin were investigated. As the results, GLF performed significant hyaluronidase inhibition ability (IC50 = 0.272 mg/mL), alleviated the allergic reactions of RAW 264.7 macrophage cells via decreasing the secretion of TNF-α and NO by 58.75 % and 46.17 %, respectively, and mitigated the degranulation degree and secretion of IL-4, TNF-α and histamine as well as promoted IL-10 secretion in RBL-2H3 mast cells. In BALB/c mouse, after gavage of GLF, the mouse allergic symptoms got significantly alleviated, the secretion of IgE and IgG1 got reduced, IgG2a got promoted, the IL-4 secretion from mouse spleen lymphocytes (SLP) significantly declined, and IL-10 and IFN-γ secretion in SLP got improved, which indicated GLF performed significantly anti-allergic functions via transforming Th2 response into Th1 and Treg response. Moreover, the SLP cells treated by GLF had lower expression of GATA-3, higher T-bet and Foxp3 expression, which indicated GLF could mitigate allergic reactions via regulating T-bet, GATA3 and Foxp3 transcription factor expression of T cell subsets. Therefore, GLF could serve as anti-allergic substances for shrimp-induced allergy via regulating Th1/Th2 cytokines and T cell subsets.

Amino acid-mTOR pathway-associated transcription factor GATAβ4 regulates storage protein expression in Bombyx mori.

Storage proteins (SPs) are hexameric macromolecular protein, an important component of insect serum protein, which plays a variety of roles in insect metamorphosis and development. However, their regulatory mechanisms remain unclear. Our previous studies revealed that the expression of SPs is regulated by nutritional signals and identified FoxO as a negative regulator of SPs in the silkworm Bombyx mori (B. mori). In this study, amino acids upregulated BmSP expression, whereas Rapamycin downregulated it in fat body cultured in vitro. Rapamycin also reduced BmSP expression in B. mori larvae. Overexpression of the nutrient transcription factor GATA family in BmE cells revealed that only BmGATAβ4 significantly upregulated BmSP expression. Furthermore, the amino acid-mTOR signaling pathway modulated BmGATAβ4 expression. Overexpression of BmGATAβ4 resulted in increased BmSP expression in B. mori larvae. Luciferase reporter assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation identified GATA-like CRE 1-1 and GATA-like CRE 2-2 of the BmSP1 promoter as binding sites for BmGATAβ4. These findings provide new insights into the regulation of nutrient protein expression in insects.

Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM.

The GATA factor AreB regulates nitrogen metabolism, fungal development, and aflatoxin production in Aspergillus flavus.

Nitrogen is important for fungal growth and development, and the GATA transcription factor AreA has been widely studied as a key regulator of nitrogen catabolite repression (NCR) in many fungi. However, AreB, another GATA transcription factor in the NCR pathway, remains less studied, and its role in Aspergillus flavus is still unclear. In this study, we characterized areB in A. flavus and investigates its role in regulating nitrogen utilization, fungal growth, and aflatoxin production. The areB gene produces three transcripts, with areB-α being the most abundantly expressed, particularly under nitrogen-limited conditions. Gene expression analysis via qPCR confirmed that areB acts as a negative regulator of NCR, as its deletion led to the upregulation of NCR-related genes under nitrogen-limiting conditions. Gene function analysis of areB revealed that its deletion impaired hyphal growth, reduced conidia production, and delayed conidial germination. Additionally, deletion of areB led to increased aflatoxin production, particularly under less favorable nitrogen sources, while overexpression of areB reduced aflatoxin levels. Furthermore, areB influenced sclerotia formation in a nitrogen-source-dependent manner. These findings reveal the multifaceted role of areB in nitrogen regulation, fungal development, and secondary metabolism, offering insights for controlling aflatoxin contamination and fungal growth.

The GATA-3-dependent transcriptome and tumor microenvironment are regulated by eIF4E and XPO1 in T-cell lymphomas.

The transcription factor GATA-3 and the transcriptional program it regulates have emerged as oncogenic drivers across diverse T-cell lymphomas (TCL), many of which are resistant to conventional chemotherapeutic agents and characterized by recurrent losses of key tumor suppressor genes, including TP53 and PTEN, both of which are clients of the nuclear export protein XPO1. Here we demonstrated that XPO1 is highly expressed by malignant T cells expressing GATA-3 and by lymphoma-associated macrophages (LAM) within their tumor microenvironment (TME). Using complementary genetically engineered mouse (GEM) models, we demonstrated that TP53 and/or PTEN deficient TCL, and LAM within their TME, are sensitive to the selective XPO1 antagonist selinexor. In an effort to identify TP53 and PTEN independent mechanisms, we used complementary and orthogonal approaches to investigate the role of eIF4E and XPO1-dependent mRNA nuclear export in these TCL. We identified a novel role for eIF4E/XPO1 in exporting GATA-3 and GATA-3-dependent transcripts from the nucleus in TCL, and in the export of therapeutically relevant transcripts, including CSF-1R, from LAM. Therefore, XPO1 antagonism, by impairing oncogenic transcriptional programs in TCL and depleting LAM from their TME, is a novel approach to target two independent dependencies in a group of therapeutically challenging TCL.

An update on epigenetic mechanisms in endometriosis.

The etiopathogenesis of endometriosis, a chronic debilitating disease affecting nearly 10% of women, has evaded elucidation until the recent epigenetic discoveries. Although still deemed multifactorial, endometriosis is likely predisposed in women with genetic and epigenetic alterations, which are activated by environmental factors. There are many epigenetic changes that have recently been associated with endometriosis: DNA methylation and phosphorylation, modifications to histones and non-coding RNA, and chromatin remodeling and organization. Gene markers, such as HOXA10, SF-1, and GATA transcription factors, are also debatably correlated to endometriosis. An improved understanding of the etiopathogenesis of endometriosis may propel our field toward our objectives: sooner and more efficient detection as well as targeted therapy. In this comprehensive review, we will identify and discuss the current literature on epigenetic changes seen in endometriosis. A primary computerized search was performed on PubMed and Google scholar of publications from 1990 to 2022. We searched for keyword terms such as "endometriosis" and "endometriosis epigenetics." We also looked through the references of prior articles to find other relevant articles to this topic. Articles were categorized by type of epigenetic change found such as DNA hypo- or hyper- methylation, histone hyper- or hypo-acetylation, chromatin remodeling, and non-coding RNA-mediated down-regulation and the research was elaborated in sections based on the type of epigenetic change. There are many articles on TET, DNMTs, EZH2, HDACs, HATs, let-7 family, miRNAs, Hox proteins, GATA family, sirtuins (e.g. SIRT1, SIRT3), ARID1A, SF-1, USF1, USF2, STRA6, ESR1, ESR2, PGR, ALDHIA2, and CTCF; however, the studies analyzed in this review were heterogeneous in comparison populations, analysis methods, tissues types (e.g. endometriomas, ectopic endometriotic tissue, eutopic endometrial tissue). Due to this, it is difficult to synthesize over-arching conclusions based on the current literature; however, there are many epigenetic changes and genes linked to endometriosis as noted in the literature.

A GATA transcription factor contributes to the multidrug resistance and pathogenicity though mediating the transcription of hydrolases and xenobiotic detoxification genes in Sclerotinia sclerotiorum

A GATA transcription factor contributes to the multidrug resistance and pathogenicity though mediating the transcription of hydrolases and xenobiotic detoxification genes in Sclerotinia sclerotiorum

Comparative analysis of amino acid sequence level in plant GATA transcription factors

Transcription factors (TFs) are essential regulators of gene expression, influencing numerous biological processes such as development, growth, and cellular responses in plants. Among these, GATA TFs are distinguished by their highly conserved DNA-binding domain, characterized by a class IV zinc finger motif (CX2CX18-20CX2C). This study investigates the amino acid sequence patterns of 5,335 GATA TFs across 165 plant species sourced from the PlantTFDB database (http://planttfdb.gao-lab.org/), encompassing diverse taxonomic groups. Through comparative sequence analysis, I identify conserved domains and structural features that enhance the understanding functional roles, evolutionary conservation, and lineage-specific adaptations of GATA TFs. These findings provide valuable insights into the diversification and functional specialization of GATA TFs, with implications for improving stress tolerance and adaptability in crops. This study contributes to the broader knowledge of transcriptional regulation in plant biology.

Spatiotemporal dynamics of the developing zebrafish enteric nervous system at the whole-organ level.

Neural crest cells give rise to the neurons of the enteric nervous system (ENS) that innervate the gastrointestinal (GI) tract to regulate gut motility. The immense size and distinct subregions of the gut present a challenge to understanding the spatial organization and sequential differentiation of different neuronal subtypes. Here, we profile enteric neurons (ENs) and progenitors at single-cell resolution during zebrafish embryonic and larval development to provide a near-complete picture of transcriptional changes that accompany the emergence of ENS neurons throughout the GI tract. Multiplex spatial RNA transcript analysis identifies the temporal order and distinct localization patterns of neuronal subtypes along the length of the gut. Finally, we show that functional perturbation of select transcription factors Ebf1a, Gata3, and Satb2 alters the cell fate choice, respectively, of inhibitory, excitatory, and serotonergic neuronal subtypes in the developing ENS.

Proteome and metabolome of Annona crassiflora Mart. fruit and their interaction during development

Marolo (Annona crassiflora Mart.) is an exotic fruit from the Brazilian Cerrado, rich in various bioactive compounds. This unprecedented study analyzed through different techniques (spectrophotometric methods, UPLC, HS-SPME-GC–MS) the proteomic and metabolic changes in four distinct stages of development, their biochemical correlations, biological processes and how proteins are dynamized promoting such processes and biosynthetic pathways. Among the four stages, 993 proteins were identified and 45 metabolites were quantified. At the beginning of development there is a greater presence of ribosomal, transcriptional and post-translational proteins, to increase the protein synthetic machinery that must coordinate the other biological processes essential for development. The families of transcription factors GATA, MADS-Box, MYB, F-box and HD-Zip were identified, which are likely coordinators of the biological processes of marolo together with phytohormones. At the ripe stage, there is an increase in the accumulation of some cellulases to intensify the softening of the fruit, and the antioxidant system of marolo presented a mostly constant behavior, in order to control the steady states of the naturally produced reactive oxygen species. Several proteins identified are related to the detected metabolites, with emphasis on the production and regeneration of vitamin C and the carotenogenic pathway. The volatile profile of marolo was related to the action of some enzymes and the supremacy of volatile esters. Therefore, proteomics in conjunction with metabolomics allowed us to have a molecular view of how compounds and proteins are produced during marolo development and how the behavior of proteins appears to influence biological processes and pathways.

Dissecting roles of pannier splice variants during pupal and adult morphogenesis in Henosepilachna vigintioctopunctata.

The GATA transcription factor gene, pannier (pnr), has been extensively studied in Drosophila, revealing its crucial role in dorsal closure, heart development and the regulation of cuticular bristle patterns in adults. However, studies on the functions of pnr in the development of coleopteran insects are still scarce. Herein, we identified the pnr gene in Henosepilachna vigintioctopunctata and discovered two splicing variants named Hvpnr-α and Hvpnr-β respectively. Temporal expression analysis revealed that Hvpnr, Hvpnr-α and Hvpnr-β were expressed at various stages including egg, larval, pupal and adult stages. To investigate the developmental role of Hvpnr in H. vigintioctopunctata, RNA interference (RNAi) assays were conducted on third-instar larvae. Injection of dsHvpnr, dsHvpnr-α and dsHvpnr-β and co-injection of dsHvpnr-α and dsHvpnr-β (dsRNAs mix) all resulted in significant downregulation of the target transcripts. In pupae developed from dsHvpnr-treated larvae, the symmetric black spots on both sides of the mesothorax, metathorax and tergites approached and connected. Pupal morphometric analysis revealed that dsHvpnr, dsHvpnr-α and dsRNAs mix injections significantly narrowed the spacing of dorsal symmetric spots, contracted spiracle distances on tergite sides, diminished pronotum width and markedly reduced inter-compound eye spacing compared to controls. In addition, injections of dsHvpnr and dsRNAs mix significantly reduced the oviposition in female adults. Silencing of Hvpnr led to the disappearance of the scutellum in adults, preventing the elytra from closing and properly attaching to the dorsal side of the abdomen. It is noteworthy that dsHvpnr-α or dsRNA mix induced scutellum formation defects in adults, while knockdown of Hvpnr-β had no impact. Furthermore, in stark contrast to previous studies on ladybird species such as Harmonia axyridis and Coccinella septempunctata, silencing Hvpnr did not affect melanin synthesis in pupae and adults in H. vigintioctopunctata. These findings demonstrate that among the splice variants of Hvpnr, Hvpnr-α plays a dominant regulatory role in the post-embryonic morphogenesis of H. vigintioctopunctata. This study also shows that Hvpnr is not involved in melanin synthesis, indicating significant functional differentiation of pnr during the evolution of ladybirds.

Transcriptional Regulation of the Human MGP Promoter: Identification of Downstream Repressors.

Matrix Gla protein (MGP) is a vitamin K-dependent γ-carboxylated protein that was initially identified as a physiological inhibitor of ectopic calcification, primarily affecting cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for the Keutel syndrome, a condition characterized by abnormal calcifications in the cartilage, lungs, brain, and vascular system. MGP has been shown to be dysregulated in several tumors, including cervical, ovarian, urogenital, and breast cancers. Using bioinformatic approaches, transcription factor binding sites (TFBSs) containing CpG dinucleotides were identified in the MGP promoter, including those for YY1, GATA1, and C/EBPα. We carried out functional tests using transient transfections with a luciferase reporter assay, primarily for the transcription factors YY1, GATA1, C/EBPα, and RUNX2. By co-transfection analysis, we found that YY1, GATA1, and C/EBPα repressed the MGP promoter. Furthermore, the co-transfection with RUNX2 activated the MGP promoter. In addition, MGP expression is negatively or positively correlated with the studied TFs' expression levels in several cancer types. This study provides novel insights into MGP regulation by demonstrating that YY1, GATA1, and C/EBPα are negative regulators of the MGP promoter, and DNA methylation may influence their activity. The dysregulation of these mechanisms in cancer should be further elucidated.

The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling.

Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion oncoproteinCBFβ::MYH11 regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBFβ::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBFβ::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy.

KIF20A activated by transcription factor GATA2 promotes cell growth in hepatitis B virus-related hepatocellular carcinoma.

Elevated evidence suggests that KIF20A plays an important role in hepatocellular carcinoma (HCC) progression. Nevertheless, the underlying mechanism by which KIF20A promotes HCC cell growth are not well understood. Using TCGA-LIHC RNAseq and GEO datasets, we assessed the KIF20A expression and patient survival in HCC and hepatitis B virus (HBV)-related HCC. Mutant and CNV analysis were performed to evaluate the genetic alteration of KIF20A in HCC. PPI network and GSEA enrichment was utilized for analyzing the KIF20A-related genes and involved pathways in HCC. To further explore regulatory mechanism in HBV-related HCC, PROMO prediction and luciferase reporter system was utilized for verifying HBx/GATA2/KIF20A binding sites. CCK-8 and flow cytometry were carried out to determine the regulation of GATA2-KIF20A on HBV-related HCC cell proliferation and apoptosis. KIF20A was significantly upregulated in pan-cancer (including HCC). KIF20A mRNA level was a significant independent predictor of overall survival in HBV-related HCC patients. Genetic alterations analysis revealed the copy number gain and amplification triggered KIF20A upregulation in HCC. In addition, the genes associated with KIF20A expression in HCC was enriched in PLK1 pathway and cell cycle in HCC. HBx might indirectly binds to KIF20A promoter via regulating GATA2. Additionally, transcription factor GATA2 directly binds to the promoter region of KIF20A. Overexpression of GATA2 promotes HepG2.2.15 cell growth and inhibits cell apoptosis via modulating KIF20A. Our findings demonstrated that HBx contributed to cell proliferation by interacting with GATA2 and KIF20A in HBV-related HCC.

The molecular mechanisms of steroid hormone effects on cognitive function

ObjectiveThere is a lack of information on the molecular mechanisms by which steroid hormones (testosterone, estrogen, and progesterone) regulate cognitive impairment. Thus, we aimed to identify the protective effects of steroid hormones on cognitive function. MethodsWe analyzed the literature on the molecular mechanisms, biological activities, physicochemical properties, and pharmacokinetics of steroid hormones. ResultsSteroid hormones can protect against cognitive impairment by regulating key genes (INS, TNF, STAT3, ESR1). Specific microRNAs, namely hsa-miR-335-5p, hsa-miR-16-5p, and hsa-miR-26b-5p, along with transcription factors NFKB1, PPARG, NR3C1, GATA2, EGR1, ATF3, and CEBPA, play a significant role in this protective mechanism. The involvement in cognitive processes, regulation of phosphorylation, neuronal apoptosis, and signaling pathways related to Alzheimer's disease significantly influence the protein-protein interaction network underlying these effects. Additionally, steroid hormones exhibit anti-hypercholesterolemic properties, anti-inflammatory activity, antitoxic properties, and function as inhibitors of acetylcholine neuromuscular transmission. They also hold promise as therapeutic agents for the treatment of dementia. Promising therapeutic interventions for cognitive impairment include the use of miRNA sponges targeting hsa-miR-16-5p, along with the administration of capsaicin, minocycline, dopamine, sertraline, and minaprine. The gut microbiota species Lactobacillus amylovorus, Paraprevotella clara, Libanicoccus massiliensis, Prevotella oris, Turicibacter sanguinis, and Dubosiella newyorkensis were identified as significant contributors to cognitive impairment and altered levels of steroid hormones. ConclusionSteroid hormones are promising compounds for improving cognitive function. Further research is needed to validate these findings through focused investigations into apoptosis, regulation of neuronal cell death, miRNA sponges, interactions with gut microbiota, and the potential efficacy of pharmaceutical agents.

ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33

Suppression of Tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor/ Toll-like receptor superfamily, and its specific ligand is Interleukin-33 (IL-33). IL-33/ ST2 signaling has been implicated in numerous inflammatory and allergic diseases, as well as in promoting malignant behavior of tumor cells and angiogenesis. However, the precise role of ST2 in gastric cancer angiogenesis remains incompletely elucidated. We observed a significant correlation between high expression of ST2 in gastric cancer tissues and poor prognosis, along with various clinicopathological features. In vitro experiments demonstrated that the IL-33/ ST2 axis activates the PI3K/AKT/NF-κB signaling pathway through TRAF6, thereby promoting VEGFA-mediated tumor angiogenesis; meanwhile sST2 acts as a decoy receptor to regulate the IL-33/ST2L axis. Consistent findings were also observed in subcutaneous xenograft tumor models in nude mice. Furthermore, we investigated the molecular mechanism by which IL-33 promotes ST2L expression in GC cells via upregulation of transcription factors YY1 and GATA2 through intracellular signaling pathways.

Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast

Macrosomia, which is frequently associated with gestational diabetes mellitus (GDM), is linked to maternal glycemic control during gestation. When GDM is complicated by macrosomia (GDMM), the placenta exhibits increased mass, underscoring its role as a critical nexus for maternal-fetal nutrient exchange. Despite this recognized correlation, the underlying mechanisms propelling placental hypertrophy have remained elusive. Our study leveraged single-cell RNA transcriptome sequencing of GDMM placental tissues to pinpoint the specific syncytiotrophoblast (SCT) subsets that regulate placental dimensions. Notably, we observed pronounced upregulation of the epidermal growth factor receptor (EGFR) and its corresponding ligands, with a particular emphasis on the autoregulatory cascade involving the glycoprotein hormone alpha subunit (CGA), EGFR, and the transcription factor GATA binding protein 2 (GATA2), as well as perturbations in hormonal homeostasis within the SCT. Furthermore, our cell interaction analysis revealed an enhanced interplay between myeloid cells and SCT3, augmenting the EGFR signaling pathway. These molecular exchanges underscore the pivotal role of the placental immune microenvironment in the etiology of macrosomia, shedding light on the pathophysiology of GDMM and paving the way for novel therapeutic approaches.

MiRNAs targeted transcription factors HaGATAa/b to mediate the post-mating switch in Helicoverpa armigera female reproductive behavior.

The process of mating induces significant shifts in female reproductive behavior across various species, with the postmating behavioral switch playing a crucial role in insect reproduction. Previous studies have demonstrated the regulatory role of GATA transcription factors in vitellogenin transcription and egg formation in insects, while miRNAs have been implicated in modulating GATA expression and insect reproductive processes. Nevertheless, the precise regulatory mechanism underlying the interaction between miRNAs and GATA transcription factors in the postmating behavioral switch remains largely unexplored. In this study, we identified two key GATA transcription factors, HaGATAa and HaGATAb, as central players in orchestrating the postmating behavior of H. armigera using transcriptomics and RNAi technologies. HaGATAa was found to act upstream of HaGATAb, regulating its expression. Furthermore, we observed a postmating increase in miR-282 levels in females, targeting HaGATAa to regulate egg-laying capacity. Conversely, the decreased expression of miR-2 following mating functioned as a negative feedback regulator, influencing the expression of HaGATAb and thus impacting the postmating behavior of female individuals. Our results revealed a signal-mediated feedback regulatory mechanism that sustains female postmating behavior in H. armigera. These findings not only establish a strong basis for understanding the postmating behavior mechanisms in female moths, but also offer valuable insights for identifying potential targets for pest control strategies. © 2024 Society of Chemical Industry.

IRF3 Promotes Asthma Pathogenesis by Regulating Type 2 Innate Lymphoid Cells

ABSTRACT Background Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear. Methods In this study, we investigated the expression of IRF3 in ILC2s in both human patients and mouse models of asthma. We utilized IRF3-deficient mice to assess the impact of IRF3 deficiency on ILC2 function in a model of IL33-induced asthma. Additionally, we explored the mechanisms underlying IRF3-mediated regulation of ILC2s, focusing on the involvement of the transcription factor Gata3. Results Our findings revealed elevated expression of IRF3 in ILC2s of patients and mice with asthma, suggesting a potential role for IRF3 in the pathogenesis of allergic asthma. Furthermore, we demonstrated that IRF3 deficiency impairedthe expansion and function of ILC2s in IL33-induced asthma, highlighting the importance of IRF3 in regulating ILC2-mediated responses. Importantly, we showed that the regulation of ILC2s by IRF3 was independent of Th2 cells and mediated by the transcription factor Gata3. Conclusion This study identifies IRF3 as a novel regulator of lung ILC2s and suggests its potential as a promising immunotherapeutic target for allergic asthma. These findings shed light on the intricate mechanisms underlying asthma pathogenesis and provide insights into potential strategies for the development of targeted therapies for this prevalent airway disease.

Comparative Analysis of Transcription Factors TWIST2, GATA3, and HES5 in Glioblastoma Multiforme : Evaluating Biomarker Potential and Therapeutic Targets Using In Silico Methods.

Glioblastoma multiforme (GBM) is characterized by substantial heterogeneity and limited therapeutic options. As molecular approaches to central nervous system (CNS) tumors have gained prominence, this study examined the roles of three genes, TWIST2, GATA3, and HES5, known to be involved in oncogenesis, developmental processes, and maintenance of cancer stem cell properties, which have not yet been extensively studied in GBM. This study is the first to present gene expression data for TWIST2, GATA3, and HES5 specifically within the context of GBM patient survival. Gene expression data for TWIST2, GATA3, and HES5 were collected from GBM and normal brain tissues using datasets from The Cancer Genome Atlas (TCGA) via the Genomic Data Commons (GDC) portal and the Genotype-Tissue Expression (GTEx) database. These data were rigorously analyzed using in silico methods. All three genes were significantly more expressed in GBM tissues than in normal tissues. TWIST2 and GATA3 were linked to lower survival rates in GBM patients. Interestingly, higher HES5 levels were associated with better survival rates, suggesting a complex role that needs more investigation. This study shows that TWIST2, GATA3, and HES5 could help predict outcomes in GBM patients. Our multigene model offers a better understanding of GBM and points to new treatment options, bringing hope for improved therapies and patient outcomes. This research advances our knowledge of GBM and highlights the potential of molecular diagnostics in oncology.