Expression Data from JAM-C or TAZ overexpressing ARPE-19 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE251997 | GEO | 2025/12/30
REPOSITORIES: GEO
Similar Datasets
Project description:Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis. Transcriptome analysis using RNA-sequencing (RNA-Seq) revealed that AIM2 was significantly downregulated in primary human RPE (phRPE) cells undergoing EMT and proliferation. Consequently, Aim2-deficient mice showed morphological changes and increased FN expression in RPE cells under physiological conditions, whereas AIM2 overexpression in phRPE cells inhibited EMT. In a retinal detachment-induced PVR mouse model, AIM2 deficiency promotes RPE-EMT, resulting in severe experimental PVR. Clinical samples further confirmed the downregulation of AIM2 in the PVR membranes from patients. Kyoto Encyclopedia of Genes and Genome analysis revealed that the PI3K-AKT signaling pathway was significantly related to RPE-EMT and that AIM2 inhibited AKT activation in RPE cells by reducing its phosphorylation. Moreover, treatment with eye drops containing an AKT inhibitor alleviated RPE-EMT and the severity of experimental PVR. These findings provide new insights into the complex mechanisms underlying RPE-EMT and PVR pathogenesis, with implications for rational strategies for potential therapeutic applications in PVR by targeting RPE-EMT.
2024-12-23 | GSE282859 | GEO
Project description:Endothelial cells form a barrier between the components present in the blood and the underlying tissue. Essential to formation of this barrier are junctional complexes present between cells. These complexes are dynamic, tightly regulated and remodel during key physiological processes such as inflammation, angiogenesis and development to allow passage of molecules, cells and movement of endothelial cells. One such junctional protein, Jam-C, is involved in the pathology of a number of inflammatory disease states and its inhibition in vitro and in vivo results in aberrant forms of leukocyte migration, dysregulated angiogenesis and inhibition of cell migration. Intracellular trafficking has been shown to be a general means of regulating the function of junctional proteins but its role in Jam-C function is unclear. Using a combination of receptor mutagenesis, HRP and APEX-2 proximity labelling alongside light and electron microscopy, we here characterise the dynamics and route of Jam-C trafficking. Rather than trafficking with junctional proteins associated with the inflammatory process, Jam-C co-traffics with receptors associated with changes in permeability such as VE-Cadherin, NRP-1 and 2. We show that Jam-C becomes ubiquitylated by the E-3 ligase CBL and that this post translational modification controls the likelihood of its degradation in the lysosomes or its recycling back to the cell surface. Finally, we show that Jam-C trafficking is essential for some of the endothelial functions of Jam-C.
2019-11-06 | PXD013003 | Pride
Project description:Retinal pigment epithelium (RPE) stress and injury often leads to epithelial to mesenchymal transition (EMT), in which RPE cells lose its cobblestone morphology and acquire more motile and spindle-shaped fibroblast phenotype. RPE dysfunction due to acquired EMT phenotype have been implicated in a number of retinal diseases such as proliferative vitreoretinopathy (PVR), diabetic retinopathy (DR), neovascular (“wet”) and atrophic (“dry”) age-related macular degeneration (AMD). We investigated distinct temporal protein expression changes and signaling events that occur during enzymatically dissociated hRPE EMT model, as well as those that occur up to forty-eight hours after EMT onset. Further, we compared analysis on altered proteome profiling with malignancy associated EMT and AMD models. Together, proteome profiles provide a comprehensive RPE EMT resources for understanding molecular signaling events, associated biological pathways, that underlie RPE-EMT onset and further identifying chemical modulators that could potentially inhibit RPE EMT.
2021-09-21 | PXD019600 | Pride
Project description:Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity. Keywords: HepG2 cells
2007-07-01 | GSE6080 | GEO
Project description:Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity. Experiment Overall Design: HepG2 cells were transduced with lentiviruses and stably selected using puromycin. Comparison of four controls and five JAM-A knockdown samples.
2008-06-14 | E-GEOD-6080 | biostudies-arrayexpress
Project description:Identification of interactors is a major attempt in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here we aim to identify novel interacting binding partners for the β-galactoside-binding proteins Galectin-1 (Gal-1) and Galectin-3 (Gal-3) in context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion and epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes. Gal-1 and Gal-3 bind in a dose- and carbohydrate-dependent manner to mesenchymal RPE cells and inhibit cellular processes like attachment and spreading. Yet knowledge about glycan-dependent interactors of Gal-1 and Gal-3 on RPE cells is very limited, although this is a prerequisite to unravel the influence of galectins on distinct cellular processes in RPE cells. In this approach, we identified by galectin pull-down experiments and quantitative proteomic screening 131 Galectin-3 and 15 Galectin-1 interactors. They mainly play a role in multiple binding processes and are mostly membrane proteins. Here we focused on two novel identified interactors of Gal-1 and Gal-3 in the context of PVR: the low-density lipoprotein receptor LRP1 and the platelet-derived growth factor receptor beta PDGFRB. We observed crosslinking and lattice formation of exogenous Gal-1 and Gal-3 with LRP1/PDGFRB and ITGB1 on the cell surface of human RPE cells. Weaker binding of Gal-1 and Gal-3 on these interactors and no lattice formation on the cell surface was seen, when complex-type-N-glycosylation was inhibited by treatment of the cells with Kifunensine. In conclusion, the identified specific glycoprotein ligands for Gal-1 and Gal-3 give us new insights in the highly specific binding of galectins to dedifferentiated RPE cells and the resulting prevention of PVR-associated cellular events.
2017-06-06 | PXD005461 | Pride
Project description:Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions such as macular pucker and proliferative vitreoretinopathy. We found that co-treatment with TGFβ1 and TNFα (TNT) accelerates EMT in adult human RPE stem cell (RPESC)-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these factors, inhibits key transcriptional changes and prevents and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.
2020-04-22 | GSE128143 | GEO
Project description:Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions such as macular pucker and proliferative vitreoretinopathy. We found that co-treatment with TGFβ1 and TNFα (TNT) accelerates EMT in adult human RPE stem cell (RPESC)-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these factors, inhibits key transcriptional changes and prevents and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.
2020-04-22 | GSE128142 | GEO
Project description:Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF–β) and the inflammatory cytokine tumor necrosis factor alpha (TNF–α), can induce RPE–EMT; however, small molecule inhibitors of RPE–EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKβ) that selectively targets NF-κB signaling, can modulate TGF–β/TNF–α-induced RPE–EMT. Next, we performed RNA-seq studies on BAY651942 treated hRPE monolayers to dissect altered biological pathways and signaling events. Further, we validated the effect of IKKβ inhibition on RPE–EMT-associated factors using a second IKKβ inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE–EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT.
2024-04-08 | GSE228934 | GEO
Project description:Junction Adhesion Molecule-A (JAM-A) is present on leukocytes and platelets where it promotes cell adhesion and motility. We are interested in an interaction between JAM-A and tumor progression/metastases. To address this point, we mated JAM-A-/- mice and mouse mammary tumor model MMTV-PyMT mice which, which express polyoma middle T antigen under the control of mouse mammary tumor virus. MMTV-PyMT mice show 100% penetration of mammary tumor and highly metastases to lung. MMTV-PyMT mice without JAM-A show less primary tumor progression, therefore JAM-A enhance primary tumor progression. Then we are addressing the molecular mechanism of this phenomenon by in vivo. Furthermore, we would like to examine JAM-A deficient MMTV tumor signature.
2010-10-01 | GSE22555 | GEO