Unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in acromegaly
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PROVIDER: PRJNA643979 | ENA |
REPOSITORIES: ENA
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Project description:Acromegaly is a growth hormone (GH) excess pathological condition in humans and is associated with somatic disfigurement and a wide variety of systemic manifestations such as arthritis, neuropathies, carpal tunnel syndrome, reproductive disorders, metabolic disorders, and gastrointestinal complications. Studying the effect of growth hormone (GH) excess at the cellular level could help in understanding the underlying causes of acromegaly complications. In our previous publications, we have shown that excess GH increases DNA damage and impairs DNA repair pathways in somatic cells. In addition, we revealed that excessive GH reduces the number of stem cells and causes premature aging. Exaggerated growth is one of the main features of acromegaly and therefore, in this research, we have focused on protein production and biogenesis in acromegaly and whether excess GH is associated with unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. Acromegaly-associated abnormal growth can be caused by hypertrophy or hyperplasia. Using pathway enrichment analysis of RNA seq data from our Zebrafish Acromegaly Model and Flow Cytometry Analysis, here we show a progressive increase in hepatocyte cell size and enrichment of hypertrophy pathways in the muscle and liver. That was associated with a progressive enrichment of protein production pathways and ribosome biogenesis. Moreover, using GSEA (Gene Set Enrichment Analysis) of acromegaly RNA seq data, here we show that endoplasmic reticulum (ER) stress is an accompanying feature of acromegaly disease. Our model exhibited endoplasmic reticulum (ER) stress in various organs, especially in the brain.
2021-03-04 | GSE153755 | GEO
Project description:We are currently studying how these information-carrying oligosaccharides are involved in cellular stress responses, particularly in human genetic diseases called Congenital Disorders Of Glycosylation in which oligosaccharide assembly is defective. We are interested in endoplasmic stress responses/unfolded protein responses. ER glycans and ER lectins are intimately involved in the folding of ER proteins. Therefore, ER lectins and ER glycosyltransferases may be controlled by these stress responses, to produce and/or recognize key glycans in the stress response. Our model system is the human dermal fibroblast. We have successfully calibrated the ER stress responses in these cells by determining the magnitudes of various stress effects (such as chaperone transcription) with different forms of ER stress. We are also completing a study in which activation the signaling molecules Ire1 and ATF6 are also calibrated. We prepared multiple identical aliquots of RNA from cells stressed under several of these calibrated conditions. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR): Study of the role of ER stress in the expression of genes for ER transferases and lectins that participate in ER folding and quality control using human skin fibroblasts. The UPR response in these cells has been calibrated using various readouts in response to different stresses: 1) 40 nM L-azetidine-2-carboxylate (AZC) 1 hour, 2) 0.2 mg/ml castanospermine, 24 hours, 3) 2 mM Dithiothreitol (DTT), 20 minutes, 4) 100nm Thapsigargin (TG), 30 minutes, 5) 5 ug/ml tunicamycin, 5 hours, 6) untreated control cells
2011-02-17 | E-GEOD-27349 | biostudies-arrayexpress
Project description:We set out to determine the role of the IRE1/XBP1 pathway, the most ancient and highly conserved endoplasmic reticulum (ER) stress-sensing pathway of the unfolded protein response (UPR), in Schmid metaphyseal chondrodysplasia (MCDS). RNA derived from hypertrophic zones microdissected from growth plates of wildtype mice, mice lacking XBP1 activity in chondrocytes (Xbp1Cart?Ex2), mice carrying a COL10A1 pN617K mutation (ColXN617K), and compound mutants (C/X) was analyzed by whole genome microarray analysis. 1633 probes were differentially expressed between ColXN617K and wildtype, 215 probes were differentially expressed between Xbp1Cart?Ex2 and wildtype, and 1337 probes were differentially expressed between C/X and wildtype. 885 probes were differentially expressed between ColXN617K and wildtype but not Xbp1Cart?Ex2 and wildtype or C/X and wildtype, thus representing the XBP1-dependent response to hypertrophic chondrocyte ER stress. 688 probes were differentially expressed between ColXN617K and wildtype and between C/X and wildtype but not Xbp1Cart?Ex2 and wildtype, thus representing the XBP1-independent response to hypertrophic chondrocyte ER stress. Results were validated by qPCR. Entire growth plate hypertrophic zones were microdissected from one tibia from each of three 2-week old wildtype mice, three 2-week old mice carrying a COL10A1 p.N617K mutation (ColXN617K), three 2-week old mice lacking XBP1 activity in chondrocytes (Xbp1Cart?Ex2), and three 2-week old mice resulting from a cross between ColXN617K and Xbp1Cart?Ex2 (C/X).
2015-08-21 | E-GEOD-72261 | biostudies-arrayexpress
Project description:We are currently studying how these information-carrying oligosaccharides are involved in cellular stress responses, particularly in human genetic diseases called Congenital Disorders Of Glycosylation in which oligosaccharide assembly is defective. We are interested in endoplasmic stress responses/unfolded protein responses. ER glycans and ER lectins are intimately involved in the folding of ER proteins. Therefore, ER lectins and ER glycosyltransferases may be controlled by these stress responses, to produce and/or recognize key glycans in the stress response. Our model system is the human dermal fibroblast. We have successfully calibrated the ER stress responses in these cells by determining the magnitudes of various stress effects (such as chaperone transcription) with different forms of ER stress. We are also completing a study in which activation the signaling molecules Ire1 and ATF6 are also calibrated. We prepared multiple identical aliquots of RNA from cells stressed under several of these calibrated conditions.
2011-02-17 | GSE27349 | GEO
Project description:We set out to determine the role of the IRE1/XBP1 pathway, the most ancient and highly conserved endoplasmic reticulum (ER) stress-sensing pathway of the unfolded protein response (UPR), in Schmid metaphyseal chondrodysplasia (MCDS). RNA derived from hypertrophic zones microdissected from growth plates of wildtype mice, mice lacking XBP1 activity in chondrocytes (Xbp1CartΔEx2), mice carrying a COL10A1 pN617K mutation (ColXN617K), and compound mutants (C/X) was analyzed by whole genome microarray analysis. 1633 probes were differentially expressed between ColXN617K and wildtype, 215 probes were differentially expressed between Xbp1CartΔEx2 and wildtype, and 1337 probes were differentially expressed between C/X and wildtype. 885 probes were differentially expressed between ColXN617K and wildtype but not Xbp1CartΔEx2 and wildtype or C/X and wildtype, thus representing the XBP1-dependent response to hypertrophic chondrocyte ER stress. 688 probes were differentially expressed between ColXN617K and wildtype and between C/X and wildtype but not Xbp1CartΔEx2 and wildtype, thus representing the XBP1-independent response to hypertrophic chondrocyte ER stress. Results were validated by qPCR.
2015-08-21 | GSE72261 | GEO
Project description:The unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation, a cell condition that occurs in solid tumors. A key feature of the UPR is the activation of the transcription program that allows the cell to cope with endoplasmic reticulum (ER) stress. We used micoarrays to show that the UPR transcription program is disrupted by the antitumor macrocyclic compound versipelostatin (VST) and antidiabetic biguanides metformin, buformin and phenformin, depending on cellular glucose availability. Experiment Overall Design: Total 42 samples were prepared for RNA extraction and hybridization on Affymetrix microarrays. Experiment Overall Design: To induce the UPR, we treated cells (HeLa, HT-29, HT1080, MKN74) for 15 or 18 hours under ER stress conditions by replacing the medium with glucose-free medium or by adding either 2-Deoxy-D-glucose (2DG) or Tunicamycin (TM) to glucose-containing medium. UPR modulators (VST, biguanides or pyrvinium pamoate) were added at various final concentrations immediately after cells were placed in glucose-free medium or just before the chemical stressors were added to glucose-containing culture medium.
2009-06-01 | E-GEOD-13548 | biostudies-arrayexpress
Project description:The unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation, a cell condition that occurs in solid tumors. A key feature of the UPR is the activation of the transcription program that allows the cell to cope with endoplasmic reticulum (ER) stress. We used micoarrays to show that the UPR transcription program is disrupted by the antitumor macrocyclic compound versipelostatin (VST) and antidiabetic biguanides metformin, buformin and phenformin, depending on cellular glucose availability. Keywords: stress response, drug response
2009-05-20 | GSE13548 | GEO
Project description:We obtained transcriptional profiles of third instar eye imaginal disc nuclei with or without endoplasmic reticulum stress using next generation sequencing (NGS). We employed an isolation of nuclei tagged in specific cell type (INTACT) protocol (Ma and Weake, J. of Vis. Exp., 2014) to label nuclear membranes of GMR-GAL4-expressing cells with EGFP. The experimental group also expressed a mutant allele of the membrane visual protein rhodopsin (Rh-1(G69D)), which is known to cause endoplasmic reticulum stress and initiate Unfolded Protein Response (UPR) signaling. The goal of this study was to characterize the transcriptional changes associated with endoplasmic reticulum stress responses in a commonly used platform, the eye imaginal disc.
2021-09-20 | GSE150058 | GEO
Project description:Enterovirus A71 (EV-A71) is a single-stranded, positive sense RNA virus causing endoplasmic reticulum stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). The 3A protein of EV-A71 was identified as a major regulator of the UPR caused by infection with EV-A71. To identify the molecular pathways for the 3A protein to regulate the UPR, we performed RNA sequencing (RNA-seq) with RD cells expressing the 3A protein. Wild type or defective mutant of 3A protein that carried alanine substitutions of Ile8 or Ile10 (3A-I8A or -I10A) was expressed in the cells. The RNA-seq with cells expressing either WT or mutant 3A was performed.
2024-06-16 | GSE268418 | GEO
Project description:The hepatic unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum stress that is important in the pathogenesis of many liver diseases. In this study, we utilized liver biopsies from patients after liver transplantation as a disease model to determine the transcriptional profile and hepatic UPR gene expression that is associated with liver injury and cholestasis.
2022-08-17 | GSE203453 | GEO