The gene expression changes in mouse brain lacking NDRG2
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154195 | GEO | 2025/04/30
REPOSITORIES: GEO
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Project description:The gene expression changes in mouse brain lacking NDRG2
| PRJNA645399 | ENA
Project description:Liver fibrosis resulting from chronic liver damage constitutes a major health care bur-den worldwide; however, no antifibrogenic agents are currently available. Our previ-ous study reported that the small molecule NPLC0393 extracted from the herb Gyno-stemma pentaphyllum exerts efficient antifibrotic effects both in vivo and in vitro. In this study, a TMT-based quantitative proteomic study using a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was performed to identify the potential target of NPLC0393. Combining this study with protein-protein interaction network analysis of differentially expressed proteins between the CCl4 model and NPLC0393 treatment groups, we focused on the function of NDRG2 involved in cell differentia-tion. In vitro studies showed that NPLC0393 prevented the TGF-β1 stimula-tion-induced decrease in the NDRG2 level in hepatic stellate cells (HSCs). Functional studies indicated that NDRG2 can inhibit the activation of HSCs by preventing the phosphorylation of ERK and JNK. Furthermore, knockdown of NDRG2 abolished the ability of NPLC0393 to inhibit HSC activation. In conclusion, these results pro-vide information on the mechanism underlying the antifibrotic effect of NPLC0393 and shed new light on the potential therapeutic function of the TGF-β1/NDRG2/MAPK signaling axis in liver fibrosis.
2021-09-09 | PXD019448 | Pride
Project description:Purpose: The most clearly established genetic hallmark in oligodendroglial tumors (OTs) is the combined loss of 1p/19q, a molecular alteration characteristic of tumors responding to therapy. Markers of tumoral progression have not yet been studied. Experimental Design: Novel markers of tumoral progression in OTs were sought through gene expression profiling analysis. Results: Unsupervised hierarchical cluster analysis classified OTs into two main groups associated with tumoral grade, independent of histological subtype and 1p/19q status. Differential gene expression analysis between low- and high-grade OTs revealed that only cell cycle-related genes were significantly upregulated in high-grade OTs. Among the deregulated genes, NDRG2 downregulation was detected in high-grade OTs with combined loss of 1p/19q. Expression analysis revealed low transcript levels of NDRG2 relative to non-tumoral brain tissue in 45% (9/20) of high-grade OTs. Furthermore, the low transcript levels of NDRG2 were significantly associated with a worse clinical outcome in patients. Transcript levels of NDRG2 were associated with promoter hypermethylation, which was detected in 38.4% (10/26) of high-grade OTs. The treatment of glioma cell lines T98 and LN18 with demethylating agents increased the mRNA expression levels of NDRG2 relative to the control cell line. Additionally, cell proliferation was significantly reduced and cell cycle was arrested in G1 phase after treatment with demethylating agents. Conclusions: Taken together, our results suggest that NDRG2 is a candidate tumor suppressor gene in OTs whose inactivation could be involved in tumoral progression and worse patient survival.
2011-02-09 | GSE27005 | GEO
Project description:N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule. We showed that astrocytic Ndrg2 can function as a modulator of the BBB permeability following ischemic stroke in mice. To further identify the Ndrg2-dependent pathways, we compared global expression profiles of ischemic brains in Ndrg2KO mice and in wild-type mice.
2025-04-30 | GSE99288 | GEO
Project description:Purpose: The most clearly established genetic hallmark in oligodendroglial tumors (OTs) is the combined loss of 1p/19q, a molecular alteration characteristic of tumors responding to therapy. Markers of tumoral progression have not yet been studied. Experimental Design: Novel markers of tumoral progression in OTs were sought through gene expression profiling analysis. Results: Unsupervised hierarchical cluster analysis classified OTs into two main groups associated with tumoral grade, independent of histological subtype and 1p/19q status. Differential gene expression analysis between low- and high-grade OTs revealed that only cell cycle-related genes were significantly upregulated in high-grade OTs. Among the deregulated genes, NDRG2 downregulation was detected in high-grade OTs with combined loss of 1p/19q. Expression analysis revealed low transcript levels of NDRG2 relative to non-tumoral brain tissue in 45% (9/20) of high-grade OTs. Furthermore, the low transcript levels of NDRG2 were significantly associated with a worse clinical outcome in patients. Transcript levels of NDRG2 were associated with promoter hypermethylation, which was detected in 38.4% (10/26) of high-grade OTs. The treatment of glioma cell lines T98 and LN18 with demethylating agents increased the mRNA expression levels of NDRG2 relative to the control cell line. Additionally, cell proliferation was significantly reduced and cell cycle was arrested in G1 phase after treatment with demethylating agents. Conclusions: Taken together, our results suggest that NDRG2 is a candidate tumor suppressor gene in OTs whose inactivation could be involved in tumoral progression and worse patient survival. The microarray study involved 28 glioma samples including oligodendrogliomas and oligoastrocytomas WHO grade II and III. Six non-tumoral brain tissues were used as controls, two of which were purchased from Stratagene (La Jolla, CA) and Clontech (Mountain View, CA). RNAs from several cell lines (Universal Human RNA, Stratagene, La Jolla, CA) was used as a standard reference in all hybridizations
2011-02-09 | E-GEOD-27005 | biostudies-arrayexpress
Project description:Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina
2015-09-16 | E-GEOD-62854 | biostudies-arrayexpress
Project description:We found that the circadian protein PER2 interacts with the nuclear receptor PPARgamma to repress its activity. PPARgamma is a master regulator of adipogenesis and lipid metabolism and is very abundant in adipose tissue. We used microarrays to detail the global program of gene expression in adipose tissue lacking the per2 gene. This analysis identified several PPARgamma target genes up-regulated in adipose tissue from per2-/- mice. Per2-/- and per2+/+ male mice (Bae et al., 2001) were housed under 12 hr light/12 hr dark (LD) cycles. Mice 20 weeks old were sacrificed at the same time and adipose tissue (WAT and BAT) was collected for RNA extraction. 3 biological replicates per mouse/tissue.
2010-10-19 | E-GEOD-20165 | biostudies-arrayexpress
Project description:We performed single-cell RNA sequencing on bone marrow derived, cultured dendritic cells after CRISPR-knockout of Ndrg2, after vitamin D3 treatment or no treatment. In addition we performed single-cell RNA sequencing of wounds that had been treated with hydrogels seeded with Ndrg2-KO dendritic cells, control (untreated) dendritic cells or blank hydrogels.
2023-06-09 | GSE234145 | GEO
Project description:Trophoblast differentiation from human ESC has been achieved by exposing the cells to BMP4 with or without supplementation of ALK4/5/7 inhibitor (A83-01) and FGF2 signaling inhibitor (PD173074) (BAP). Here the two differentiation conditions, BMP4 and BAP were applied to two sets of human PSC lines, H1 ESC and iPSC that latter was generated by DOX-inducible lentiviral (V) transductions of umbilical cord mesenchymal cells. The V-iPSC showed residual transgene expressions from the viral vectors in DOX-free culture condition. When the both ESC and iPSC lines were differentiated simultaneously, similar time dependent morphological changes were observed but BMP4 treated V-iPSC showed a minor yet consistent lag in the differentiation progression compared to BMP4 treated hESC. Although both differentiated ESC and V-iPSC showed dominant trophoblast phenotypes, the BMP4 treated V-iPSC also expressed gene markers consistent with the presence of mesoendoderm. The BAP condition provided more efficient differentiation than BMP4 alone, and the BAP-differentiated iPSC and ESC never expressed mesoendoderm markers.
2015-08-31 | GSE64272 | GEO
Project description:In the brain, focal ischemia results in a local region of cell death and disruption of both local and remote functional neuronal networks. Tissue reorganization following stroke can be limited by factors such as extracellular matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The brain's ECM plays a crucial role in network formation, development, and regeneration of the central nervous system. Further, the ECM is essential for proper white matter tract development and for the formation of structures called perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory interneurons, of importance for processing sensory information. Previous studies have shown that downregulating PNNs after stroke reduces the neurite-inhibitory environment, reactivates plasticity, and promotes functional recovery. Resting-state functional connectivity (RS-FC) within and across hemispheres has been shown to correlate with behavioral recovery after stroke. However, the relationship between PNNs and RS-FC has not been examined. Here we studied a quadruple knock-out mouse (Q4) that lacks four ECM components: brevican, neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and 14 days after photothrombotic stroke (PT) to understand how the lack of crucial ECM components affects neuronal networks and functional recovery after stroke. Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC compared to wild-type mice, especially in the sensory and parietal regions. Changes in RS-FC were significantly correlated with the number of interhemispheric callosal crossings in those same regions. PT caused unilateral damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing ability in contralesional fore- and hindlimbs, but the two experimental groups did not present significant differences in infarct size. Two weeks after PT, a general down-scaling of regional RS-FC as well as the number of regional functional connections was visible for all cortical regions and most notable in the somatosensory areas of both Q4 and wild-type mice. Q4 mice exhibited higher intrahemispheric RS-FC in contralesional sensory and motor cortices compared to control mice. We propose that the lack of growth inhibiting ECM components in the Q4 mice potentially worsen behavioral outcome in the early phase after stroke, but subsequently facilitates modulation of contralesional RS-FC which is relevant for recovery of sensory motor function. We conclude that Q4 mice represent a valuable model to study how the elimination of ECM genes compromises neuronal function and plasticity mechanisms after stroke.
| S-EPMC5851486 | biostudies-literature