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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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TGF or TNF Time series in ARPE19

ABSTRACT: Aberrant epithelial-mesenchymal transition (EMT) is involved in pathological processes including fibrotic disorders and cancer invasion and metastasis. Alterations of the cell-extracellular matrix (ECM) interaction also contribute to those pathological settings. However, the functional interplay between EMT and cell-ECM interaction is poorly understood. Here, we show that tumor necrosis factor (TNF)-alpha, a potent mediator of inflammation, induces EMT-associated fibrosis in retinal pigment epithelial cells, and that this is regulated by hyaluronan (HA)-CD44-Moesin interaction. TNF-alpha elicits both HA synthesis and Moesin phosphorylation through protein kinase C activation, promoting binding of CD44 to the newly synthesized HA. The HA-CD44-Moesin interaction leads to cell-cell dissociation through actin remodeling and increased cellular motility associated with mesenchymal phenotype. Furthermore, we established an in vivo model of TNF-alpha-induced fibrosis in the mouse eye, and the ocular fibrosis was completely suppressed in CD44-null mice. Therefore, HA production and its interaction with CD44 plays essential role in TNF-alpha-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders. ARPE19 cell lines were treated with TGF and TNF for 6 and 42 hour. Each experiment were repeated three times. But 1hour experiment was repeated two times. For this submission, total RNA was extracted from TGF- or TNF-treated ARPE-19 cells and differential gene expression between each time point (6 and 42 hours) was determined using genechip arrays (Affymetrix, Human Genome U133).

ORGANISM(S): Homo sapiens

SUBMITTER: Rui Ose

PROVIDER: E-GEOD-15205 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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TGF or TNF Time series in ARPE19

Project description:Aberrant epithelial-mesenchymal transition (EMT) is involved in　pathological processes including fibrotic disorders and cancer invasion and metastasis. Alterations of the cell-extracellular matrix　(ECM) interaction also contribute to those pathological settings.　However, the functional interplay between EMT and cell-ECM　interaction is poorly understood. Here, we show that tumor necrosis factor (TNF)-α, a potent mediator of inflammation, induces　EMT-associated fibrosis in retinal pigment epithelial cells, and that this is regulated by hyaluronan (HA)-CD44-Moesin interaction. TNF-α elicits both HA synthesis and Moesin phosphorylation through protein kinase C activation, promoting binding of CD44 to the newly synthesized HA. The HA-CD44-Moesin interaction leads to cell-cell dissociation through actin remodeling and increased cellular motility associated with mesenchymal phenotype. Furthermore, we　established an in vivo model of TNF-α-induced fibrosis in the mouse eye, and the ocular fibrosis was completely suppressed in CD44-null mice. Therefore, HA production and its interaction with CD44 plays essential role in TNF-α-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders.

2010-03-11 | GSE15205 | GEO

Modeling of Aberrant Epithelial Reprogramming in Idiopathic Pulmonary Fibrosis using Human Induced Pluripotent Stem Cell-derived Alveolar Organoids

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Project description:To identify the cytokines secreted by mesenchymal-like cancer cells that activate macrophages, the cytokine profiles of conditioned media from MCF7, MCF7 induced to undergo EMT by treatment of TGF-β, TNF-α and prolonged mammosphere culture, and MDA-MB-231 cells were analyzed by RayBio® Human Cytokine Antibody Array V. 5 samples. There are 5 groups: MCF7, MCF7 induced to undergo EMT by treatment of TGF-β (TGF-β-MCF7), TNF-α (TNF-α-MCF7), prolonged mammosphere culture (MCF7M), and MDA-MB-231 cells

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2021-12-13 | GSE164160 | GEO

Bi-directional epithelial-mesenchymal crosstalk provides self-sustaining pro-fibrotic signals in pulmonary fibrosis

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2021-08-19 | PXD025821 | Pride

Dissociating fibrosis from inflammation in systemic sclerosis – the case of interleukin-17A

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2020-02-11 | GSE122305 | GEO

Transcription profiling of human GFAP-negative lamina cribrosa cells TGF-beta regulated gene transcription and protein expression

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beta 1 integrin signaling governs necroptosis via the chromatin remodeling factor CHD4

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2023-10-30 | PXD041505 | Pride

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