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Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 3)

ABSTRACT: To clarify the role of monocyte in the pathogenesis of SSc, we analyzed gene and protein expression in monocyte from SSc and healthy controls in order to identify the molecules which were associated with pathogenesis of SSc. After the screeining using gene and protein expression profiles, functional role of the candidate molecules were further analyzed to clarify the role in the pathogenesis of SSc.

ORGANISM(S): Homo sapiens

SUBMITTER: Hidekata Yasuoka

PROVIDER: E-GEOD-44998 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 1)

Project description:To clarify the role of monocyte in the pathogenesis of SSc, we analyzed gene and protein expression in monocyte from SSc and healthy controls in order to identify the molecules which were associated with pathogenesis of SSc. After the screeining using gene and protein expression profiles, functional role of the candidate molecules were further analyzed to clarify the role in the pathogenesis of SSc.

2013-03-12 | E-GEOD-44996 | biostudies-arrayexpress

Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 2)

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Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-03-12 | E-GEOD-44999 | biostudies-arrayexpress

Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 1)

2013-03-12 | GSE44996 | GEO

Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 3)

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Gene expression profile in CD14+ monocytes in patients with SSc or healthy controls (part 2)

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Gene expression in limited cutaneous SSc skin

Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by clinical heterogeneity, multi-organ involvement, and complex genetic risk. Here, we report the first multi-tissue meta-analysis of ten independent SSc gene expression datasets. We identify a common immune-fibrotic expression axis across all tissues that is associated with the most severe disease phenotypes. The coexpression patterns conserved across tissues and phenotypes were used to query functional genomic networks, which allowed us to identify common and tissue-specific disease drivers. We find evidence of pro-fibrotic macrophages (MØs) in SSc end-target organs. Prominent genes in the skin functional genomic network are associated with SSc genetic risk and are modulated by immunosuppressive treatment in clinical improvers. These data suggest the interactions between T lymphocytes and MØs are a critical driver of disease and implicate MØs as central to SSc pathogenesis. In total, this study presents a mechanism for fibrosis in SSc end-target tissues, a set of putative therapeutic targets for modulating SSc, and a framework for multi-tissue functional genomic studies of complex human disease.

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Periostin may act on monocytes and monocyte-derived macrophages with a pro-fibrotic phenotype in patients with systemic sclerosis (SSc)

Project description:Background: Circulating periostin levels are increased in systemic sclerosis (SSc) patients and correlates positively with disease severity. Additionally, monocytes/macrophages are one of the key cells in SSc pathogenesis. However, the effect of periostin on immune cells, particularly monocytes and macrophages, has not been well investigated. Objectives: To examine the effect of periostin on monocytes and monocyte-derived macrophages (MDMs) in SSc. Methods: Monocytes were purified from blood samples of nine diffuse cutaneous SSc patients and five healthy controls (HCs) and were differentiated into macrophages. Cell surface markers were assessed by flow cytometry. RNA sequencing analysis was performed on recombinant periostin-stimulated monocytes from three HCs. Cytokine/chemokine and extracellular matrix (ECM) protein expressions in MDMs differentiated supplemented with recombinant periostin were assessed by quantitative real-time polymerase chain reaction and bead-based immunoassays in six HCs. Moreover, we evaluated whether periostin was involved in monocyte migration by Transwell assay. Results: The modified Rodnan total skin thickness score correlated positively with the proportion of CD80-CD206+ M2 cells. The M2 macrophage proportion was reduced in rPn-stimulated MDMs in HCs, but not in SSc patients. mRNA expression levels of pro-fibrotic cytokine, chemokine, and ECM protein genes were significantly upregulated in recombinant periostin-stimulated monocytes and MDMs as compared to those from control monocytes and MDMs. Similar trends for their protein levels were also observed in MDMs. Moreover, the ratio of migrated cells in recombinant periostin-stimulated monocytes was significantly higher than that in control monocytes.

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Apoptosis gene signature of Survivin and its splice variant expression in breast carcinoma

Project description:Background: Survivin was described as strongly expressed in human cancer. To date, little is known about the association between Survivin splice variants and the other apoptosis-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Methods: Expression of the 5 transcripts was measured by RT-PCR in 135 breast carcinomas. Human Apoptosis Gene Arrays were used to screen the genes that could be associated with Survivin variants. Cox survival analysis was analyzed according to the breast cancer patient outcome. Results: Significant associations between Survivin transcript and the apoptotic gene array were found. Interestingly, Survivin-3B variant showed major inverse correlations with the pro-apoptotic gene array. Overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/Cyclophosphamide induced-apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of survivin-3B expression had a shorter overall (p=0.030 and p=0.042, respectively) and disease-free (p=0.024 and p=0.009) survival. Conclusion: Our data indicate Survivin-3B could have an anti-apoptotic activity and its expression level might be used as a prognostic marker in breast carcinoma. The expression of 96 apoptosis genes and was analyzed in 41 breast carcinomas and 1 pool of normal mammary tissues. In parallel, every survivin isoform expression was quantified by real-time quantitative PCR. Data obtained with the macro-array were correlated with survivin isoform levels detected by RT-PCR.

2010-10-06 | E-GEOD-24556 | biostudies-arrayexpress