MassIVE MSV000100385

Complete Public PXD072700

Ancestry-Linked IL-10 Signaling and Macrophage Activation Modulate Fibroblast Responses to Oxidative Stress in a PEG-Based Microphysiological System

Subscribe Comment Convert Spectra Reanalyze Spectra Compare Results Add Reanalysis

Description

Fibroblast responses to injury are shaped by cytokine signaling and macrophage activation, yet the extent to which these pathways vary across individuals, and how ancestry associated immune differences influence fibrosis risk, remains poorly understood. Here, we developed a poly(ethylene glycol) (PEG)-based hydrogel microphysiological system to model fibroblast-macrophage interactions following oxidative stress and integrate donor-specific immune signals using matched macrophages and serum. Circulating monocytes from individuals of self-reported African American ancestry exhibited higher expression of CCL4 and increased serum IL10, whereas those from European ancestry donors showed elevated OXER1 expression. Within the hydrogel, oxidative stress reduced fibroblast number while inducing Ki67 and p16. Exogenous TGFbeta1 enhanced fibroblast survival and collagen 3 production but did not independently increase alpha smooth muscle actin (alphaSMA). Anti-inflammatory macrophages promoted fibroblast activation through mechanisms resistant to TGFbeta receptor inhibition. Incorporating donor-derived macrophages and serum revealed that cultures from individuals of European ancestry demonstrated higher fibroblast alphaSMA and p16 expression, despite lower systemic IL10 levels. Pharmacologic inhibition of IL10 further increased alphaSMA, particularly in European ancestry derived cultures, identifying IL10 as a key protective signal limiting fibroblast activation. This hydrogel system provides a platform for dissecting inter-individual immune variation and identifying mechanisms underlying ancestry associated fibrosis risk. [doi:10.25345/C5S17T627] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: sera ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Erika Taylor Moore, University of Maryland, United States
Submitting User: pabloprd
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files Browse Results
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.