Coordinate regulation of galectins in GAL3 deficient mouse keratinocytes exposed to UVB irradiation
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE27599 | GEO | 2011/03/02
SECONDARY ACCESSION(S): PRJNA138271
REPOSITORIES: GEO
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Project description:Dr. Liu's research group is interested in studying the expression and functions of galectin-3, -7 and -12, in particular the roles of these proteins in inflammation and neoplasm. Members of the galectin family are known to participate in cellular homeostasis by modulating cell growth, controlling cell cycle progression, and inducing or inhibiting apoptosis. It is known that some galectins have similar functions. However, it is not fully understood whether they work cooperatively or not. Recent reports suggest that gal-3 deficiency may induce changes in cellular homeostatic mechanisms, leading to changes in expression of other galectins and galectin-related proteins. To analyze the coordinate regulation of galectins in the face of gal-3 deficiency, gene expression patterns of gal-3 / and gal-3 -/- keratinocytes exposed to UVB were compared. Murine epidermal keratinocytes from gal-3 / and gal-3 -/- mice will be irradiated with 200 J/m2 of UVB. Total RNA will be extracted at 0, 6, 12 and 24 h after irradiation. Classes were prepared in triplicate for a total of 24 samples. All samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.
2011-03-02 | E-GEOD-27599 | biostudies-arrayexpress
Project description:Dr. Liu's research group is interested in studying the expression and functions of galectin-3, -7 and -12, in particular the roles of these proteins in inflammation and neoplasm. Members of the galectin family are known to participate in cellular homeostasis by modulating cell growth, controlling cell cycle progression, and inducing or inhibiting apoptosis. It is known that some galectins have similar functions. However, it is not fully understood whether they work cooperatively or not. As the outermost barrier of the body, skin is directly and frequently exposed to a prooxidative environment, including solar ultraviolet A (UVA), ultraviolet B (UVB) radiation, and air pollution. Several reports have shown that exposure of cells to UV increase or decrease the levels of galectins. For example, the amounts of galectin-7 mRNA and protein are increased rapidly after UVB irradiation of keratinocytes (Proc. Natl. Acad. Sci. USA 1999; 96:11329-34). Heat shock and subculturing decrease, while alkylating agents and UV-light increase galectin-3 (Cell Physiol Biochem 2000; 10:149-58). To analyze the change of all galectin gene expression profiles after UVB irradiation and to determine the presence or absence of coordinate regulation, we analyzed the gene expression profiles of keratinocytes exposed to UVB. Normal human epidermal keratinocytes (NHEK) were irradiated with 200 J/m2 of UVB. Total RNA will be extracted at 0, 6, 12 and 24 h after irradiation (duplicate) for analysis on the Glyco gene chip.
2011-02-17 | GSE27360 | GEO
Project description:Dr. Liu's research group is interested in studying the expression and functions of galectin-3, -7 and -12, in particular the roles of these proteins in inflammation and neoplasm. Members of the galectin family are known to participate in cellular homeostasis by modulating cell growth, controlling cell cycle progression, and inducing or inhibiting apoptosis. It is known that some galectins have similar functions. However, it is not fully understood whether they work cooperatively or not. As the outermost barrier of the body, skin is directly and frequently exposed to a prooxidative environment, including solar ultraviolet A (UVA), ultraviolet B (UVB) radiation, and air pollution. Several reports have shown that exposure of cells to UV increase or decrease the levels of galectins. For example, the amounts of galectin-7 mRNA and protein are increased rapidly after UVB irradiation of keratinocytes (Proc. Natl. Acad. Sci. USA 1999; 96:11329-34). Heat shock and subculturing decrease, while alkylating agents and UV-light increase galectin-3 (Cell Physiol Biochem 2000; 10:149-58). To analyze the change of all galectin gene expression profiles after UVB irradiation and to determine the presence or absence of coordinate regulation, we analyzed the gene expression profiles of keratinocytes exposed to UVB. Normal human epidermal keratinocytes (NHEK) were irradiated with 200 J/m2 of UVB. Total RNA will be extracted at 0, 6, 12 and 24 h after irradiation (duplicate) for analysis on the Glyco gene chip. Several reports have shown that exposure to UV light can regulate levels of galectin in skin. This study seeks to analyze the changes in all galectin gene expression profiles post-UVB irradiation to determine the presence or absence of coordinate regulation. In this study, normal human keratinocytes were irradiated with 200J/m2 of UVB. Total RNA was extracted at 0, 6, 12, and 24-hour post irradiation time points, in duplicate. Samples were hybridized and analyzed using the GLYCOv2 array.
2011-02-17 | E-GEOD-27360 | biostudies-arrayexpress
Project description:Galectins are a group of carbohydrate binding proteins with immunomodulatory functions. While the effects of galectins on the T cell compartment are well described, the interactions between galectins and antigen-presenting cells (APCs) remain elusive. Here we find increased expression of galectin-1(gal-1) in the stroma of a large selection of cancers, and investigating the effect of gal-1 on stroma localized antigen presenting cells, including monocyte derived dedritic cells and M1 and M2 macrophages (M1s and M2s, respectively). Using an in depth and dynamic proteomic and phosphoproteomic analysis of the effect of gal-1 on M2s we show that gal-1 induces global changes in the proteomic and signaling landscape of M2s, consistent with induction of a tolerogenic macrophage phenotype. Specifically, gal-1 induces expression of key immunomodulatory and tumor-associated proteins, including the key immune checkpoint protein, programmed cell death 1 ligand 1 (PD-L1/CD274) and the immunomodulator, indoleamine 2,3-dioxygenase-1 (IDO1). Gal-1 induced IDO1 and its active metabolite kynurenine in a dose dependent manner, an effect that was prevented by JAK/STAT inhibition. Analyzing gal-1 expression in human tumors we find that gal-1 is upregulated across multiple tumors, and in a 3D organotypic model system equipped with genetically engineered tumorigenic epithelial cells, we find that the tumor associated gal-1 is derived from both from epithelial and stromal cells. Our results highlight the potential of targeting gal-1 in immunotherapeutic treatment of human cancers.
2023-08-14 | PXD034623 | Pride
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:Inflammatory chemo- and cytokines and matrix-degrading proteases underlie the progression of osteoarthritis (OA). Aiming to define upstream regulators for these disease markers, we pursued initial evidence for an upregulation of members of the adhesion/growth-regulatory galectin family. Immunohistochemical localization of galectin-3 (Gal-3) in sections of human cartilage with increasing levels of degeneration revealed a linear correlation reaching a chondrocyte positivity of 60%. Presence in situ was cytoplasmic, in OA chondrocyte cultures the lectin was secreted and binding of Gal-3 yielded lactose-inhibitable surface staining. Exposure of cells to the lectin led to enhanced gene expression and secretion of functional disease markers. Genome-wide transcriptomic analysis broadened this insight to reveal a pro-degradative/inflammatory gene signature under the control of NF-κB. Fittingly, targeting this route of activation by inhibitors impaired the unfavourable response to Gal-3 binding, as also seen by shortening the lectin’s collagen-like repeat region. Gal-3’s activation profile overlaps with that of homodimeric galectin-1 (Gal-1) and also has distinctive (supplementing) features. Tested at subsaturating concentrations in a mixture, we found cooperation between the two galectins, apparently able to team up as driving forces in OA pathogenesis. In summary, our results suggest that a network of endogenous lectins acts as upstream master regulator in OA.
2017-02-09 | GSE85254 | GEO
Project description:Dr. Panjwani's laboratory is focusing on the mechanism by which galectins-3 and 7 mediate corneal epithelial cell migration. Recently published studies, that we have confirmed and expended on in our laboratory, clearly demonstrate that galectin-3 mediates angiogenesis in vitro and in vivo. More interestingly we have found that bFGF- and VEGF-mediated angiogenesis can be inhibited by galectin-3 inhibitors, which suggests an important role of carbohydrate recognition systems in the process of angiogenesis. In an effort to characterize the role of carbohydrate recognition system in angiogenesis, we are interested to evaluate and compare the glyco-gene expression profile of endothelial cells stimulated with VEGF, bFGF and galectin-3 at time and concentration at which, the compounds stimulate angiogenesis in vitro.
2011-04-29 | GSE28943 | GEO
Project description:Dr. Panjwani's laboratory is focusing on the mechanism by which galectins-3 and 7 mediate corneal epithelial cell migration. Recently published studies, that we have confirmed and expended on in our laboratory, clearly demonstrate that galectin-3 mediates angiogenesis in vitro and in vivo. More interestingly we have found that bFGF- and VEGF-mediated angiogenesis can be inhibited by galectin-3 inhibitors, which suggests an important role of carbohydrate recognition systems in the process of angiogenesis. In an effort to characterize the role of carbohydrate recognition system in angiogenesis, we are interested to evaluate and compare the glyco-gene expression profile of endothelial cells stimulated with VEGF, bFGF and galectin-3 at time and concentration at which, the compounds stimulate angiogenesis in vitro. RNA preparations of Galectin-3, VEGF, bFGF, Media Control biological replicates were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
2011-04-29 | E-GEOD-28943 | biostudies-arrayexpress
Project description:The reading of glycan-encoded signals by tissue lectins is considered a major route of the flow of biological information in many (patho)physiological processes. The arising challenge for current research is to proceed from work on a distinct protein to family-wide testing of lectin function. Having previously identified homodimeric galectin-1 and chimera-type galectin-3 as molecular switches in osteoarthritis progression, we here provide proof-of-principle evidence for an intra-network cooperation of galectins with three types of modular architecture. We show that the presence of tandem-repeat-type galectin-8 significantly correlated with cartilage degeneration and that it is secreted by osteoarthritic chondrocytes. Glycan-inhibitable surface binding of galectin-8 to these cells increased gene transcription and the secretion of functional disease markers. The natural variant galectin-8 (F19Y) was less active than the prevalent form. Genome-wide array analysis revealed induction of a pro-degradative/inflammatory gene signature, largely under control of NF-κB signaling. This signature overlapped with respective gene-expression patterns elicited by galectins-1 and -3, but also presented supplementary features. Functional assays with mixtures of galectins that mimic the pathophysiological status unveiled cooperation between the three galectins. Our findings shape the novel concept to consider individual galectins as part of a so far not realized teamwork in osteoarthritis pathogenesis, with relevance beyond this disease.
2021-02-17 | GSE131822 | GEO
Project description:Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are conserved carbohydrate-binding proteins that also display RNA-binding activity. We generated mouse embryonic stem cells (mESC) constitutively depleted of Gal-1 and/or Gal-3 using CRISPR-Cas9, and assessed the transcriptomic effects of the individual or concomitant depletion of Gal-1 and Gal-3 in mESCs differentiated by deprivation of the leukaemia inhibitory factor (LIF) for 7 days. Wild-type cells were employed as control.
2023-05-27 | E-MTAB-9262 | biostudies-arrayexpress