Multiomic study of skin/peripheral blood cell transcriptome and serum proteins: Is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179153 | GEO | 2021/10/20
REPOSITORIES: GEO
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Project description:BackgroundSerum proteins can be readily assessed during routine clinical care. However, it is unclear to what extent serum proteins reflect the molecular dysregulations of peripheral blood cells (PBCs) or affected end-organs in systemic sclerosis (SSc). We conducted a multiomic comparative analysis of SSc serum profile, PBC, and skin gene expression in concurrently collected samples.MethodsGlobal gene expression profiling was carried out in skin and PBC samples obtained from 49 SSc patients enrolled in the GENISOS observational cohort and 25 unaffected controls. Levels of 911 proteins were determined by Olink Proximity Extension Assay in concurrently collected serum samples.ResultsBoth SSc PBC and skin transcriptomes showed a prominent type I interferon signature. The examination of SSc serum profile revealed an upregulation of proteins involved in pro-fibrotic homing and extravasation, as well as extracellular matrix components/modulators. Notably, several soluble receptor proteins such as EGFR, ERBB2, ERBB3, VEGFR2, TGFBR3, and PDGF-Rα were downregulated. Thirty-nine proteins correlated with severity of SSc skin disease. The differential expression of serum protein in SSc vs. control comparison significantly correlated with the differential expression of corresponding transcripts in skin but not in PBCs. Moreover, the differentially expressed serum proteins were significantly more connected to the Well-Associated-Proteins in the skin than PBC gene expression dataset. The assessment of the concordance of between-sample similarities revealed that the molecular profile of serum proteins and skin gene expression data were significantly concordant in patients with SSc but not in healthy controls.ConclusionsSSc serum protein profile shows an upregulation of profibrotic cytokines and a downregulation of soluble EGF and other key receptors. Our multilevel comparative analysis indicates that the serum protein profile in SSc correlates more closely with molecular dysregulations of skin than PBCs and might serve as a reflection of disease severity at the end-organ level.
| S-EPMC8518248 | biostudies-literature
Project description:Multiomic study of skin/peripheral blood cell transcriptome and serum proteins: Is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?
| PRJNA742420 | ENA
Project description:ObjectivesTo mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment.MethodsPatients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included. They were classified as cases if they had PAH confirmed by right heart catheterisation (RHC) and serum collected on the same day as RHC; and as controls if they had no clinical evidence of PAH.ResultsPatients were mostly middle-aged females with anticentromere-associated SSc. Among 1129 proteins assessed by a high-throughput proteomic assay (SOMAscan), only 2 were differentially expressed and correlated significantly with pulmonary vascular resistance (PVR) in SSc-PAH patients (n=15): chemerin (ρ=0.62, p=0.01) and SET (ρ=0.62, p=0.01). To validate these results, serum levels of chemerin were measured by ELISA in an independent cohort. Chemerin levels were confirmed to be significantly higher (p=0.01) and correlate with PVR (ρ=0.42, p=0.04) in SSc-PAH patients (n=24). Chemerin mRNA expression was detected in fibroblasts, pulmonary artery smooth muscle cells (PA-SMCs)/pericytes and mesothelial cells in SSc-PAH lungs by single-cell RNA-sequencing. Confocal immunofluorescence revealed increased expression of a chemerin receptor, CMKLR1, on SSc-PAH PA-SMCs. SSc-PAH serum seemed to induce higher PA-SMC proliferation than serum from SSc patients without PAH. This difference appeared neutralised when adding the CMKLR1 inhibitor α-NETA.ConclusionChemerin seems an interesting surrogate biomarker for PVR in SSc-PAH. Increased chemerin serum levels and CMKLR1 expression by PA-SMCs may contribute to SSc-PAH pathogenesis by inducing PA-SMC proliferation.
| S-EPMC9918672 | biostudies-literature
Project description:Previous microarray analysis of skin biopsies from patients enrolled in the FaSScinate clinical trial revealed pathways modulated by treatment and associated with aggressive disease course. To further our understanding of these pathways, we performed RNA-seq on patients enrolled in the FocuSSced clinical trial to confirm the previous finding and explore new treatment modulated pathways.
2023-07-26 | GSE231692 | GEO
Project description:Diethlstilbestrol (DES) is a synthetic estrogen prescribed to several millions of pregnant women worldwide. The risk for breast cancer after age 40 in women prenatally exposed to DES has been reported, however, the precise mechanism of susceptibilities to breast cancer remains to be resolved. To understand the mechanism of effect of intrauterine exposure to DES on human mammary glands at peripubertal stage, we investigated the global gene expression profile of terminal end buds (TEBs), the target of carcinogen, in rat mammary glamds at postnatal days (PND) 35 and 49, equivalent to peripubertal stage in human, exposed to low or high dose of DES at neonatal period. In all group, the number of TEBs was gradually increased and peaked at PND35 and decreased at PND49. At PND 35 and 49, low dose of DES-treated group showed highest number of TEBs. At PND35, β- and γ-casein mRNA expression inreased 8.19-fold and 26.05-fold, respectively, and the most significant network revealed by IPA analyses showed relevance of NF-κB in low dose of DES-treated group. The present findings suggested that deregulation of mammary gland differentiation and development-related genes group may contribute to the increase of number of TEBs at critical period of carcinogen susceptibilities. Experiment: We used laser capture microdissection to specifically isolate the cells from terminal end buds (TEBs) in rat mammary gland at 35 and 49 days after birth. Inbred Sprague-Dawley female rats were subcutaneously given 0.05ml sesame oil (group I, control) and either 1 μg (group II) or 100 μg (group III) diethlstilbestrol (DES, Sigma Chemical Co., St. Louis, Mo. USA) dissolved in 0.05 ml sesame oil within 24 hr of birth. Animal were weaned at 21 days of birth and each group of rats was autopsied at 35 and 49 days of birth. From group I (35 days of birth: n=2, 49 days of birth: n=2), group II (35 days of birth: n=2, 49 days of birth: n=2), group III (35 days of birth: n=2, 49 days of birth: n=2), we performed a hybridization, respectively.
2010-11-06 | E-GEOD-25043 | biostudies-arrayexpress
Project description:Background. This study examines the effect of breakdown in the organ donation process on the availability of transplantable organs. A process breakdown is defined as a deviation from the organ donation protocol that may jeopardize organ recovery. Methods. A retrospective analysis of donation-eligible decedents was conducted using data from an independent organ procurement organization. Adjusted effect of process breakdown on organs transplanted from an eligible decedent was examined using multivariable zero-inflated Poisson regression. Results. An eligible decedent is four times more likely to become an organ donor when there is no process breakdown (adjusted OR: 4.01; 95% CI: 1.6838, 9.6414; P < 0.01) even after controlling for the decedent's age, gender, race, and whether or not a decedent had joined the state donor registry. However once the eligible decedent becomes a donor, whether or not there was a process breakdown does not affect the number of transplantable organs yielded. Overall, for every process breakdown occurring in the care of an eligible decedent, one less organ is available for transplant. Decedent's age is a strong predictor of likelihood of donation and the number of organs transplanted from a donor. Conclusion. Eliminating breakdowns in the donation process can potentially increase the number of organs available for transplant but some organs will still be lost.
| S-EPMC4407530 | biostudies-literature
Project description:We measured global mRNA expression in peripheral blood mononuclear cells (PBMC) from 76 individuals, comprising of 49 multiple sclerosis (MS) patients affected with distinct MS clinical forms and 27 healthy controls.
2017-09-30 | E-MTAB-5151 | biostudies-arrayexpress
Project description:Aging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats' chronological age, the majority are specific to one organ. These may be a consequence of the organ's physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats.
| S-EPMC4802414 | biostudies-literature
Project description:Aging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats’ chronological age, the majority are specific to one organ. These may be a consequence of the organ’s physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats.
2015-09-22 | GSE66715 | GEO
Project description:RNA-Seq and ribosome profiling describes changes in gene expression during aging RNA-Seq and ribosome profiling from matched young and old rat liver and brain
2015-09-22 | E-GEOD-66715 | biostudies-arrayexpress