Mus musculus
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ABSTRACT:
PROVIDER: PRJNA103899 | ENA |
REPOSITORIES: ENA
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Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis Two series of 4 mice each were treated with either control adenovirus (AdNull) or adenovirus expressing neurotrophin p75 receptor (AdP75). Anaesthetized mice received 3 adenovirus injections (for a total of 109 p.f.u. virus in 20 micro L) into 3 equidistant sites of the normoperfused or ischemic left adductor muscles, as described (2. Emanueli C, Graiani G, Salis MB, Gadau S, Desortes E, Madeddu P. Prophylactic gene therapy with human tissue kallikrein ameliorates limb ischemia recovery in type 1 diabetic mice. Diabetes. 2004 Apr;53(4):1096-103. )
2010-06-25 | E-GEOD-9910 | biostudies-arrayexpress
Project description:It has been reported that hepatic stellate cells (HSCs) differentiate from mesodermal-derived submesothelial cells during embryonic development, and that these cells express a common surface marker p75 neurotrophin receptor (p75NTR). We sorted p75NTR-expressing cells in embryonic liver at each developmental stage, and transcription profiles were analyzed using the DNA microarray.
2019-09-27 | GSE128895 | GEO
Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis
2008-07-17 | GSE9910 | GEO
Project description:Effect of neurotrophin receptor p75 (p75NTR) over-expression on the miRNAome of human umbilical vein endothelial cells
| PRJNA233661 | ENA
Project description:Background In the present study, we explore the intricate relationship between the adult hippocampal neurogenesis and the p75 pan-neurotrophin receptor (p75NTR), under physiological or neurodegenerative conditions, focusing on Alzheimer's Disease (AD). The hippocampal adult neurogenesis, the process of generating new neurons in the Dentate Gyrus (DG), is crucial for cognitive function and emotional resilience. Dysregulation of this process is strongly implicated in AD, a neurodegenerative disorder characterized by cognitive decline and memory impairment. p75NTR, known for its diverse functions in neuronal survival, differentiation and synaptic plasticity, emerges as a key player in modulating adult neurogenesis. In addition, its significant role in the context of AD has recently been revealed, although the exact mechanism of action remains elusive. Methods This study aims to address the connective relation of adult hippocampal neurogenesis and AD by investigating the role of the p75NTR in mouse and human neural stem cells under physiological and AD conditions. Results We firstly evaluated the impact of p75NTR in in vivo adult hippocampal neurogenesis, by performing 5-bromo-2′-deoxyuridine (BrdU) injections for detection of proliferation and immunohistochemistry analysis for key neurogenic markers in p75NTR knock-out (ko) mice, compared to the wildtype of 2-, 4-, and 6- months old mice, revealing the necessity of p75NTR, and defining its cell non-autonomous function to control neural stem cell fate. In order to investigate the role of p75NTR in AD, we have generated a mouse model by crossing the p75NTR ko mice with the 5xFAD mouse, an amyloid beta dependent mouse model of AD. Our data clearly indicate the importance of p75NTR expression for the proliferation and differentiation processes of adult neural stem cells (NSCs). Differential gene expression analysis confirmed the aforementioned properties. Finally, we investigate the p75NTR effects in human induced Pluripotent Stem Cells (hiPSCs)-derived NSCs, depicting receptor’s signaling and its dysregulation in the presence of toxic Amyloid- β in human neuronal cells. Conclusions By unraveling the pleiotropic mechanisms underlying p75NTR activation in adult neurogenesis, our research seeks to offer insights into novel mechanism of action for this neurotrophin receptor, providing potential therapeutic targets for addressing AD-related neurogenesis deficits.
2026-04-01 | GSE296390 | GEO
Project description:Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple targets in the brain to regulate cognitive functions, and are compromised in numerous neurodegenerative disorders. Our previous study showed that injury to the target region of these neurons affects their viability in vivo. Moderate cortical injury in mice promoted a significant increase in proneurotrophins in the injured cortex, leading to the retrograde loss of BFCNs ipsilateral to the injury via the p75 neurotrophin receptor (p75NTR). We determined that stimulation of BFCN axon terminals with proNGF elicited retrograde degeneration of the axons leading to cell death of these neurons in vitro. Our current study investigates mechanisms of axonal p75NTR signaling, and shows that retrograde transport and local axonal protein synthesis are necessary for proNGF induced retrograde degeneration initiated at the axon terminal. Analysis of the nascent axonal proteome revealed numerous newly synthesized proteins after stimulation of axon terminals with proNGF. Pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator. Our results show a functional role for APP in promoting proNGF induced BFCN axonal degeneration and cell death.
2025-05-06 | PXD043846 | Pride
Project description:Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors, tropomyosin receptor kinases (Trks) and p75NTR, have been characterised over the years, including formation of activated ligand-receptor complexes, their endocytosis, trafficking and signalling. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors to their final cellular destination are not completely understood. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of BDNF-activated TrkB and p75NTR in motor neurons. Here, we deciphered the mechanism responsible for this sorting process. Using a proteomic approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1 knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.
2020-05-26 | PXD016190 | Pride
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:P75 neurotrophin receptor regulates BMP-induced SVZ neural stem cell migration.
| PRJNA639162 | ENA
Project description: Not available
| S-EPMC11335981 | biostudies-literature