Both TRULI and DAPA may serve as anti-OA drugs by modulating ZBTB20 to restore ECM homeostasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1123580 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29386064_1.fastq.gz | Fastqsanger.gz | |||
| SRR29386064_2.fastq.gz | Fastqsanger.gz | |||
| SRR29386065_1.fastq.gz | Fastqsanger.gz | |||
| SRR29386065_2.fastq.gz | Fastqsanger.gz | |||
| SRR29386066_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:Due to the existing challenges in modulating the activity of transcription factors directly, comprehending the upstream regulatory mechanism can offer perspectives for tackling these obstacles. Our observations that in early-stage OA chondrocytes ZBTB20 translocates into nucleus in a LATS1-dependent manner, triggers NF-κB signaling and enhances ECM degradation, leads us to consider different approaches to restore ECM balance: either by inhibiting LATS1 to impede ZBTB20 activity or by directly reducing ZBTB20 expression. The small molecular compound TRULI can block the nucleus accumulation of ZBTB20 via inhibiting LATS1 phosphorylation, and DAPA was identified as a proposing drug targeting Zbtb20.Our results demonstrated that pharmacologic blockade of LATS1 by TRULI, as well as inhibition of Zbtb20 expression by DAPA, restored the ECM homeostasis in chondrocytes and minimized matrix degradation in human articular cartilage explants.
2025-03-19 | GSE269735 | GEO
Project description:Better understanding of the early molecular events and underlying mechanism will benefit the early-stage diagnose and clinical therapy of OA. In this study, we demonstrated the functions of ZBTB20 in OA pathogenesis via regulating ECM homeostasis. Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress, restored the balance of ECM anabolism and catabolism. To investigate the underlying mechanism of ZBTB20 in OA progress, RNA-seq was carried out using cultured primary chondrocytes from control and Zbtb20-cKO mice, treated by IL-1β.
2025-03-19 | GSE269579 | GEO
Project description:ZBTB20 is an adjuvant-specific factor for long-term antibody responses. This factor is critical for maintaining long-lived plasma cells in alum-adjuvanted antibody responses but is dispensable for TLR ligand-adjuvanted responses. To identify the functions of ZBTB20 in long-lived plasma cells, we performed microarray analysis on Zbtb20-sufficient and Zbtb20-deficient polyclonal bone marrow plasma cells under the assumption that ZBTB20 regulates relevant targets in all long-lived plasma cells, irrespective of their mode of formation. Chimeras were generated using Zbtb20-sufficient (WT) or Zbtb20-deficient (TRAP) E14.5 fetal livers. 3-4 months after reconstitution, donor bone marrow B220low/-CD138+ cells (4 replicates per genotype) were purified via FACS for microarray. In total, 8 samples, 4 for each genotype, were included in this study.
2014-06-19 | E-GEOD-58659 | biostudies-arrayexpress
Project description:ZBTB20 is an adjuvant-specific factor for long-term antibody responses. This factor is critical for maintaining long-lived plasma cells in alum-adjuvanted antibody responses but is dispensable for TLR ligand-adjuvanted responses. To identify the functions of ZBTB20 in long-lived plasma cells, we performed microarray analysis on Zbtb20-sufficient and Zbtb20-deficient polyclonal bone marrow plasma cells under the assumption that ZBTB20 regulates relevant targets in all long-lived plasma cells, irrespective of their mode of formation.
2014-06-19 | GSE58659 | GEO
Project description:The objective of this study was to determine if a subset of regulatory T cells (Tregs) expressing the transcription factor, Zbtb20, played a unique role in the function of the immune system. Genetic reporter mice were used to isolate Zbtb20-expressing Tregs as well as activated (CD62Llo) and naive (CD62Lhi) Tregs. The gene expression in these cells was determined with RNA-seq.
2022-02-25 | E-MTAB-11442 | biostudies-arrayexpress
Project description:The transcriptional repressor Zbtb20 is essential for specification of hippocampal CA1 pyramidal neurons. Moreover, ectopic expression of Zbtb20 is sufficient to transform subicular and retrosplenial areas of D6/Zbtb20S mice to CA1. We used microarrays to identify genes that are repressed by Zbtb20 in developing CA1 pyramidal neurons in the CA1-transformed cortex of D6/Zbtb20S mice.
2014-04-11 | GSE38837 | GEO
Project description:SUMOylation is a dynamic post-translational protein modification that primarily takes place in cell nuclei, where it plays a key role in multiple DNA-related processes. In brain cells, and particularly in neurons, mostly nuclear proteins are SUMOylated, and the SUMOylation-dependent control of a subset of neuronal transcription factors is known to regulate various aspects of nerve cell differentiation, development, and function. In an unbiased screen for endogenous SUMOylation targets in the developing mouse brain, we previously identified the transcription factor Zbtb20 as a new SUMO1 conjugate. We show here that the three key SUMO paralogues SUMO1, SUMO2, and SUMO3 can all be conjugated to Zbtb20 in vitro, and we confirm the SUMOylation of Zbtb20 in vivo. Using primary hippocampal neurons as a model system, we then demonstrate that the expression of Zbtb20 is required for proper nerve cell development and neurite growth and branching. Furthermore, we show that the SUMOylation of Zbtb20 is essential for Zbtb20 function in this context, and provide evidence indicating that SUMOylation affects the Zbtb20-dependent transcriptional profile of neurons. Taken together, our data highlight the role of SUMOylation in the regulation of neuronal transcription factors that determine nerve cell development. Specifically, our data demonstrate that key functions of the transcription factor Zbtb20 in neuronal development and neurite growth are under the obligatory control of SUMOylation.
2021-01-06 | GSE143926 | GEO
Project description:Neural precursor cells (NPCs) are multipotent cells that can generate neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system. Although Zbtb20 was expressed in NPCs, its functions in neural development are not fully understood. We performed microarray analysis to examine changes in gene expression between control and Zbtb20-overexpressed NPCs.
2016-03-17 | GSE66583 | GEO
Project description:The transcriptional repressor Zbtb20 is essential for specification of hippocampal CA1 pyramidal neurons. Moreover, ectopic expression of Zbtb20 is sufficient to transform subicular and retrosplenial areas of D6/Zbtb20S mice to CA1. We used microarrays to identify genes that are repressed by Zbtb20 in developing CA1 pyramidal neurons in the CA1-transformed cortex of D6/Zbtb20S mice. For RNA extraction and hybridization on Affymetrix microarrays, we isolated the CA1-transformed subiculum and retrosplenial cortex from postnatal day 1 D6/Zbtb20S mice, as well as corresponding areas from their wildtype littermates. Total RNA was extracted using the RNeasy Lipid Tissue Mini Kit (Qiagen). Each RNA sample represents a pool of RNA obtained from dissected tissues of seven animals.
2014-04-11 | E-GEOD-38837 | biostudies-arrayexpress
Project description:In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared to healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.
2020-01-27 | PXD012879 | Pride