Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nerve Growth Factor neutralization promotes oligodendrogenesis by increasing miR-219a-5p levels

ABSTRACT: Alterations of the crosstalk between the nervous and immune systems may underlie the inflammatory and neurodegenerative changes characterizing Multiple Sclerosis (MS). Among the molecules that actively interconnect these two systems is the Nerve Growth Factor (NGF), involved in both regulating inflammation and in brain homeostasis. Additionally, NGF is known to modulate oligodendrogenesis and reduce myelination, further suggesting an involvement of NGF in MS ethiology. In this study, we find that NGF regulates oligodendrogenesis by modulating the levels of miR-219a-5p, a well-known positive regulator of oligodendrocyte (OL) differentiation. We utilized a transgenic NGF-deprivation mouse model, AD11, in which postnatal expression of an anti-NGF antibody leads to NGF neutralization and progressive neurodegeneration. Notably, we find that these mice also display increased myelination. A microRNA profiling of AD11 brain samples (hippocampus) by Agilent microarray analysis revealed that NGF deprivation leads to an increase of miR-219a-5p levels and a downregulation of its predicted targets, compared to AD11-VH control mice. The AD11-VH controls are transgenic mice where only the heavy chain of the transgenic antibody is expressed, while in AD11 mice express the whole functional antibody (heavy + light chain)

ORGANISM(S): Mus musculus

PROVIDER: GSE162675 | GEO | 2021/02/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hypermethylation suppresses microRNA-219a-2 to activate the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis [RRBS]

Project description:Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA-219a-2 (mir-219a-2) by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyro-sequencing, we detected the hypermethylation of mir-219a-2 in renal fibrosis induced by unilateral ureter obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in mir-219a-5p expression. Functionally, overexpression of mir-219a-2 enhanced fibronectin induction during hypoxia or TGF-b1 treatment of cultured renal cells. In mice, inhibition of mir-219a-5p suppressed fibronectin accumulation in UUO kidneys. ALDH1L2 was identified to be the direct target gene of mir-219a-5p in renal fibrosis. Mir-219a-5p suppressed ALDH1L2 expression in cultured renal cells, while inhibition of mir-219a-5p prevented the decrease of ALDH1L2 in UUO kidneys. Knockdown of ALDH1L2 enhanced PAI-1 induction during TGF-b1 treatment of renal cells, which was associated with fibronectin expression. In conclusion, the hypermethylation of mir-219a-2 in response to fibrotic stress attenuates mir-219a-5p expression and induces the up-regulation of its target gene ALDH1L2, which may reduce fibronectin deposition by suppressing PAI-1.

2023-11-01 | GSE236018 | GEO

Hypermethylation suppresses microRNA-219a-2 to activate the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis [RIP-Seq]

2023-11-01 | GSE235842 | GEO

Nerve Growth Factor neutralization promotes oligodendrogenesis by increasing miR-219a-5p levels

Project description:Nerve Growth Factor neutralization promotes oligodendrogenesis by increasing miR-219a-5p levels

| PRJNA682600 | ENA

HDX-MS implicates dynamic CD20 antigen binding to two discontinuous CDR regions in the NCD1.2 monoclonal antibody

Project description:A comparative canine-human therapeutics model is being developed in B-cell lymphoma through the generation of a hybridoma cell that produces a murine monoclonal antibody specific for canine CD20. The hybridoma cell produces two light chains, light chain-3 and light chain-7. However, the contribution of either light chain to the authentic full-length hybridoma derived IgG is undefined. Mass spectrometry was used to identify only one of the two light chains, light chain-7, as predominating in the full-length IgG. Gene synthesis created a recombinant murine-canine chimeric monoclonal antibody expressing light chain-7 that reconstituted the IgG binding to CD20. Hydrogen deuterium exchange mass spectrometry was used to define two stages in the mode of binding of the CD20 epitope the antibody. In the early stage of the reaction, the antigen interacted with CDR3 (VH). In the equilibrium stages, stable binding occurred to CDR2 (VH) and CDR2 (VL), without any detectable CDR3 (VH) interactions. These data suggest that CDR3 (VH) functions as a transient antigen docking motif to nucleate the peptide into the antibody active site which resolves into antigen binding with the heavy and light chain CDR2 domains. These approaches define a methodology for fine mapping of CDR contacts using nested enzymatic reactions and hydrogen deuterium exchange mass spectrometry to map the kinetic mode of antigen binding. These data support the further development of an engineered synthetic antibody for use as a canine lymphoma therapeutic that mimics the human anti-CD20 antibody therapeutic.

2021-09-09 | PXD018550 | Pride

Hydrogen Deuterium Exchange Mass Spectrometry implicates dynamic CD20 antigen binding to two discontinuous CDR regions in the NCD1.2 monoclonal antibody

2021-09-09 | PXD018510 | Pride

miRNA expression profile in PC12 cells under NGF treatment and deprivation

Project description:miRNA profiling of PC12 rat pheochromocytoma cells during NGF-induced differentiation and apoptosis of differentiated cells after 24h of NGF deprivation. miRNA expression in differentiating and deprivated cells was compared to untreated and terminally differentiated PC12 cells respectivelly. Five-condition experiment, NGF-treated cells (1h, 3h, 6h, 24h, 240h) vs. untreated. One-condition experiment, NGF-deprivated vs. differentiated cells.

2013-05-11 | E-GEOD-46827 | biostudies-arrayexpress

Flexible chromatin loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

Project description:The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH- rearranged gene segment in the proximal Igh domain. By high-resolution mapping of long-range interactions, we now demonstrate that an array of local interaction domains establishes the three- dimensional structure of the extended Igh locus in lymphoid progenitors and thymocytes. In pro- B cells, these local domains engage in long-range interactions across the entire Igh locus, which depend on the transcription factors Pax5, YY1 and CTCF. The large VH gene cluster thereby undergoes flexible long-range interactions with the more rigidly structured 3M-bM-^@M-^Y proximal domain, which ensures that all VH genes can participate with similar probability in VH-DJH recombination to generate a diverse antibody repertoire. Notably, these long-range interactions appear to be an intrinsic feature of the VH gene cluster, as they are still generated upon mutation of the EM-NM-< enhancer, IGCR1 insulator or 3M-bM-^@M-^Y regulatory region present in the 3M-bM-^@M-^Y proximal Igh domain. 4C sequencing from mutliple celltypes with multiple viewpoints; uneven number of replicates ChIP-Seq

2013-09-30 | E-GEOD-43008 | biostudies-arrayexpress

IGH analysis in pro-B cells with H3K4me3, H3K4me2, H3K9ac, H3K27me3, Pax5 and CTCF [ChIP-chip]

Project description:VH-DJH recombination of the immunoglobulin heavy-chain (Igh) locus is temporally and spatially controlled during early B-cell development, and yet no regulatory elements other than the VH gene promoters have been identified throughout the entire 2.5-Mb VH gene cluster. Here we discovered novel regulatory sequences that are interspersed in the distal VH gene region. These conserved repeat elements were characterized by the presence of Pax5-dependent active chromatin, the binding of Pax5, E2A, CTCF and Rad21 as well as by Pax5-dependent antisense transcription in pro-B cells. The Pax5-activated intergenic repeat (PAIR) elements were no longer bound by Pax5 in pre-B and B cells consistent with the loss of antisense transcription, whereas E2A and CTCF interacted with PAIR elements throughout early B-cell development. The pro-B-cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal VH-DJH recombination at the Igh locus. Analysis of chromatin and TF binding in rag2-/- and pax5-/- rag2-/- pro-B cells. Chip-Chip with one experiment for each antibody, 12 samples.

2011-02-11 | E-GEOD-27074 | biostudies-arrayexpress

Flexible chromatin loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

Project description:The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH- rearranged gene segment in the proximal Igh domain. By high-resolution mapping of long-range interactions, we now demonstrate that an array of local interaction domains establishes the three- dimensional structure of the extended Igh locus in lymphoid progenitors and thymocytes. In pro- B cells, these local domains engage in long-range interactions across the entire Igh locus, which depend on the transcription factors Pax5, YY1 and CTCF. The large VH gene cluster thereby undergoes flexible long-range interactions with the more rigidly structured 3’ proximal domain, which ensures that all VH genes can participate with similar probability in VH-DJH recombination to generate a diverse antibody repertoire. Notably, these long-range interactions appear to be an intrinsic feature of the VH gene cluster, as they are still generated upon mutation of the Eμ enhancer, IGCR1 insulator or 3’ regulatory region present in the 3’ proximal Igh domain.

2013-09-30 | GSE43008 | GEO

miRNA expression profile in PC12 cells under NGF treatment and deprivation

2013-05-11 | GSE46827 | GEO