Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Psychological stress exacerbates vitiligo via dysregulated proteolysis of substance P and MRGPRX2-dependent mast cell activation

ABSTRACT: Although psychological stress has been anecdotally related to flare-ups of vitiligo, the underlying mechanism(s) has remained poorly defined. In this study, we investigated whether substance P (SP) and its proteolytic fragments (SP1-9 and SP1-7) modulate the anti-melanocyte immune response under stress. Dual immunofluorescence staining revealed increased SP+PGP9.5+ sensory innervation and avidin⁺ mast cell infiltration in active vitiligo lesions and in the ear skin of mice subjected to chronic restraint stress (CRS). Using a vitiligo model where mice were immunized with the Tyrp-2180-188 peptide, we demonstrated that MrgprB2-dependent mast cell activation is essential for SP- or CRS-driven disease exacerbation. In vivo intradermal administration revealed that full-length SP and the SP1-9 fragment activate mast cells and worsen depigmentation, but the SP1-7 fragment did not. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that SP proteolytic cleavage by keratinocyte-derived MMP9, rather than by fibroblast-derived neprilysin, generates elevated levels of SP1-9, which in turn activates mast cells via MRGPRX2 (mouse ortholog MrgprB2). These findings establish the SP-MRGPRX2 signaling axis as a critical link between psychological stress and vitiligo progression.

ORGANISM(S): Homo Sapiens

SUBMITTER: Tiechi Lei

PROVIDER: PXD070437 | iProX | Fri Nov 07 00:00:00 GMT 2025

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Gene expression signature from tumor initiating population predicts clinical outcome in undifferentiated pleomorphic sarcoma (UPS)

Project description:Undifferentiated pleomorphic sarcomas (UPS) are thought to harbor a small population of cells with unique capability of tumor initiation and maintenance. These tumor initiating cells (TICs) are regarded as the drivers of cancer progression. However, the evidence for this tumor initiating cell (TIC) concept is based on the xenotransplantation assays in mice and the clinical relevance of the TIC concept remains unclear in UPS. We hypothesized that the distinct properties of the TICs would be reflected in the clinical outcome if the TIC concept is relevant in UPS. Here we performed global gene expression profiling of TIC-enriched side population (SP) fractions and non-SP fractions sorted from 15 UPS primary samples. Ninety-three genes were differentially expressed in between SP fractions and non-SP fractions. The UPS TIC gene expression signature score summarizing expression of these genes was calculated for a gene expression data and was correlated with clinical outcome. In the 15 samples used to generate the signature, patients with high scores in the SP fractions were associated with worse survival. We then tested the two independent published datasets with gene expression data on bulk unsorted samples, assuming that the TIC gene expression would persist in the non-TICs. Patients with high scores had significantly worse metastasis-free survival in both datasets. The significance of the score remained significant even considering for the known prognostic factor of UPS. Thus, gene expression signature derived from UPS TICs predicts clinical outcome, suggesting the clinical relevance of the TIC concept in UPS.

2016-02-01 | GSE55973 | GEO

Single cell RNA sequencing data of Side Population and Non-Side Population tumor cells from a mouse model of undifferentiated pleomorphic sarcoma

Project description:We report the application of single-cell RNA sequencing data on Side Population (SP) cells and their Non-Side Population (NSP) counterparts in a mouse model of undifferentiated pleomorphic sarcoma (UPS). SP cells exhibit tumor propagting cell properties characterized by enhanced tumorigenicity and self-renewal potential. The purpose of this experiment is to investigate cellular heterogeneity at the gene expression level in UPS tumors and lineage relationships between different subpopulation of tumor cells. We generated the gene expression profiles of individual cells in the SP and NSP compartments of mouse UPS.

2022-01-07 | GSE162847 | GEO

A novel approach for studying mast cell-driven disorders: mast cells derived from induced pluripotent stem cells

Project description:We developed a novel strategy for the rapid and efficient differentiation of MCs from human induced pluripotent stem cells (hiPSC). These hiPSC-derived MCs (hiPSC-MCs) exhibit phenotypic and functional characteristics of human skin MCs (hsMCs) and peripheral hematopoietic stem cell-derived MCs (PSCMCs). hiPSC-MCs display stable expression of MC-associated receptors such as CD117, FcεRIα and MRGPRX2, and degranulate by stimulation with IgE/anti-IgE and Substance. P.

2022-08-31 | GSE181457 | GEO

Bone Marrow Stroma Cells: Vehicle Control vs. Substance P Treated

Project description:Gene expression profiling by cDNA microarray of bone marrow stromal cells from three healthy donors treated as follows: vehicle control; or stimulated with 10 nM substance P. Hematopoiesis is tightly regulated by the bone marrow (BM) niche. The niche is robust, allowing for the return of hematopoietic homeostasis after insults such as infection. Hematopoiesis is partly regulated by soluble factors such as neuropeptides, substance P (SP) and neurokinin A (NK-A), which mediate hematopoietic stimulation and inhibition, respectively. The hematopoietic effects of SP and NK-A are mostly mediated via BM stroma. Array analyses with 2400 genes indicated distinct changes in SP-stimulated BM stroma.

2019-05-18 | GSE131410 | GEO

Expression data from human Ea.hy926 cells in response to epoxomicin and in dependency of TCF11 presence

Project description:Coordinated regulation of the ubiquitin-proteasome system is crucial for the cell to adjust its protein degradation capacity to changing proteolytic requirements. The transcription factor TCF11 has been identified as a regulator for 26S-proteasome formation in human cells to compensate for reduced proteolytic activity. To expand the current knowledge of other UPS-related TCF11 target genes in response to epoxomicin, we performed microarray analyses of cells exposed to epoxomicin and with or without depletion of TCF11. Keywords: siRNA depletion

2010-10-08 | GSE22853 | GEO

Biomarkers of hippocampal gene expression in a mouse restraint chronic stress model

Project description:Acute stress provides many beneficial effects whereas chronic stress contributes to a variety of human health problems. The objective of this study was to use a rodent model to uncover hippocampal gene signatures associated with prolonged chronic stress which could potentially serve as biomarkers and therapeutic targets for early diagnosis and pharmacological intervention for stress induced disease. Mice were subjected to restraint stress over 7 consecutive days and gene expression changes in the hippocampus were analyzed at 3, 12 and 24 hours following the final restraint treatment. Data indicated that mice exposed to chronic restraint stress exhibit a differential gene expression profile compared to non-stressed controls. The greatest differences were observed 12 and 24 hrs following the final stress test.

2016-11-02 | E-MTAB-2402 | biostudies-arrayexpress

A SUMOylated C-terminus fragment of glutamate transporter EAAT2 linked to inherited ALS mediates motor axon impairment

Project description:Downregulation of expression and activity levels of the astroglial glutamate transporter EAAT2 is thought to be implicated in motor neuron excitotoxicity in amyotrophic lateral sclerosis (ALS). We previously reported that EAAT2 is cleaved by caspase-3 at the cytosolic C-terminus domain, impairing the transport activity and generating a proteolytic fragment found to be SUMO1 conjugated (CTE-SUMO1). We show here that this fragment accumulates in the nucleus of spinal cord astrocytes in vivo throughout the disease stages of the SOD1-G93A mouse model of ALS. In vitro expression in spinal cord astrocytes of the C-terminus peptide of EAAT2 (CTE), which was artificially fused to SUMO1 (CTE-SUMO1fus) to mimic the endogenous SUMOylation reaction, recapitulates the nuclear accumulation of the fragment seen in vivo and causes caspase-3 activation and axonal growth impairment in motor neuron-derived NSC-34 cells and primary motor neurons co-cultured with CTE-SUMO1fus-expressing spinal cord astrocytes. This indicates that CTE-SUMO1fus could trigger non-cell autonomous mechanisms of neurodegeneration. Prolonged nuclear accumulation of CTE-SUMO1fus in astrocytes leads to their degeneration, although the time frame of the cell-autonomous toxicity is longer than the one for the indirect toxic effect on motor neurons. As more evidence on the implication of SUMO substrates in neurodegenerative diseases emerges, our observations strongly suggest that the nuclear accumulation in spinal cord astrocytes of a SUMOylated proteolytic fragment of the astroglial glutamate transporter EAAT2 could take part to the pathogenesis of ALS and suggest a novel, unconventional role for EAAT2 in motor neuron degeneration in ALS. Comparison is made between the toxic fragment (SUMO) and the same fragment without lysines that can be sumo-ylated (CTE). Four replicates have been performed for each sample group.

2011-07-19 | E-GEOD-26070 | biostudies-arrayexpress

Expression data from human Ea.hy926 cells in response to epoxomicin and in dependency of TCF11 presence

2010-10-08 | E-GEOD-22853 | biostudies-arrayexpress

RNA-seq analysis between mouse UPS tumors (KP) and mouse UPS tumors without HIF-2alpha (KPH2)

Project description:Purpose: determine RNA expression differences in an unbiased fashion between UPS tumors derived from LSL-KrasG12D;Trp53-/- (KP) mice, and UPS tumors derived from LSL-KrasG12D;Trp53-/-;Epas1-/- (KPH2) mice. Epas1 encodes HIF-2alpha protein. RNA-seq was performed on KP (n = 4) and KPH2 (n = 4) derived UPS tumors using Illumina HiSeq 2000.

2015-12-31 | E-GEOD-67672 | biostudies-arrayexpress

Peripheral Substance P induces deficits in hippocampal synaptic plasticity and memory

Project description:Substance P (SP) is a neuropeptide that functions in both the central and peripheral nervous systems. Although substance P-containing neurons convey nociceptive information to the spinal cord and regulate inflammatory responses in peripheral tissues, the impact of a peripheral rise in substance P on hippocampal functions such as spatial learning and memory remains unclear. Here, we show that chronic peripheral substance P significantly impaired performance in both the object place recognition (OPR) and novel object recognition (NOR) tests compared to saline controls. Electrophysiology revealed a marked reduction in CA3‑CA1 LTP without changes in basal synaptic transmission. RNA‑Seq identified 77 differentially expressed genes (DEGs), and enrichment analysis highlighted pathways related to synaptic transmission and learning/memory.

2025-08-20 | GSE301993 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data