Contradictory Effect of ANGPTL4 on Hedgehog pathway by Galectin-7 and its Influence on Cancer metastasis and Angiogenesis
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PROVIDER: PRJNA1057263 | ENA |
REPOSITORIES: ENA
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Project description:Background: Gastric cancer (GC) is a serious malignant disease of digestive system over the world. Angiopoietin-like protein 4 (ANGPTL4) was a secreted glycoprotein, which involved in multiple pathophysiological process, such as metabolic reprogramming, angiogenesis, proliferation and metastasis. Nevertheless, the expression, function, and prognostic significance of ANGPTL4 in GC are still contradictory. Methods: Bioinformatic analysis to confirm the expression and prognosis of ANGPTLs in GC. IF staining was used to detect ANGPTL4 protein in GC samples. The molecular biological effect of ANGPTL4 was confirmed by EdU, MTT, FCS, wound healing, transwell, tube formation chorioallantoic membrane model, and nude mice model assay in GC cell lines. RNA-seq was used to confirm the potential downstream mechanism of ANGPTL4, which verified by PCR, WB, IF, co-IP and molecular docking. Results: ANGPTL4, as an important ANGPTLs, was significantly correlated with poor diagnosis in GC patients. The proliferation, migration, invasion, apoptosis escaping, angiogenesis ability was enhanced by ANGPTL4 in SNU5 and MKN7, but repressed in AGS. LGALS7 could be upregulated in AGS transfected with ANGPTL4 OE, which was one of the key factors that cause ANGPTL4 to produce an anticancer phenotype. Conclusion: LGALS7 was a key factor for the contradictory effect of ANGPTL4 on activating hedgehog pathway to driving GC progression, including proliferation, migration, apoptosis escaping, angiogenesis and lymphangiogenesis.
2024-12-01 | GSE252074 | GEO
Project description:Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy, and LGALS1-encoed galectin-1 can trigger vascular signaling programs and mediate anti-angiogenic treatment response. However, the mechanism of galectin-1 regulation of angiogenesis is poorly understood. Previous mRNA interactome studies suggested that galectin-1 associated with mRNAs. In this study, we applied the iRIP-seq methodology, an unbiased genome-wide approach to study the RNA binding profiles of galectin-1. The results demonstrate that galectin-1 interacted with a large population of mRNAs with a preferred location towards stop codon, and preferred motifs of UGCA/UGGA and GAGCAG motifs. Galectin-1-bound mRNAs are enriched in cell cycle control and diverse basic biological processes, including its previously reported protein targets H-Ras and also T cell receptors TLR6. Glectin-1 significantly binds to genes in angiogenesis, which included the key pro-angiogenic growth factor VEGFA, angiogenic regulators EGR1 and LAMA5, suggesting that galectin-1 may regulate via its mRNA binding activity. The presented results uncover an previously unrecognized mRNA binding activity of galectin-1; further pursue of this activity could lead to knowledge important for developing therapeutic strategies against cancer and other diseases involved in aberrant angiogenesis.
2021-10-14 | GSE147565 | GEO
Project description:Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.
2023-11-22 | GSE211128 | GEO
Project description:Suppression of ANGPTL4 Reprograms Endothelial Cell Metabolism and Inhibits Angiogenesis
| PRJNA869060 | ENA
Project description:ANGPTL4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4-/- mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and non-esterified fatty acid levels, strongly resembling Angptl4-/- mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4-/- mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.
2019-08-24 | GSE136240 | 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:Background: Angiogenesis is an essential step for tissue development and its dysregulation is associated with various diseases, including moyamoya disease. Among the regulators of angiogenesis, galectin-1 encoded by LGALS1, plays essential roles, but the underlying mechanisms need to be further expounded. In this study, we systematically investigated the potential targets of galectin-1 by silencing LGALS1 (siLGALS1) in human umbilical vein endothelial cells (HUVECs) and performing whole transcriptome sequencing (RNA-seq) experiments. We also integrated galectin-1-interacting RNA data to explore how galectin-1 regulates gene expression and alternative splicing. Results: By systematical analysis, we found siLGALS1 treatment significantly regulated 1451 differentially expressed genes (DEGs), including 604 up-regulated DEGs and 847 down-regulated DEGs. The down-regulated DEGs were significantly enriched in angiogenesis and inflammatory response pathways. The involved genes included CCL2, GJA5, CALCRL, ACKR3, HEY1, AQP1, CD34, ECM1, RAMP2, and SELP, which were also validated by RT-qPCR experiment. We also analyzed the dysregulated alternative splicing (AS) profile by siLGALS1, and found siLGALS1 had obvious bias for dysregulated AS types, preferring to promote exon skipping and intron retention, and inhibit cassette exon events. Interestingly, we found the regulated AS genes (RASGs) were enriched in focal adhesion and VEGF signaling pathway, which were highly related to angiogenesis. Finally, we found hundreds of RASGs were also bound by galectin-1 using the published iRIP-seq data of galectin-1, including RASGs from angiogenesis pathway. Conclusions: In summary, our results demonstrated that galectin-1 could regulate angiogenesis-related genes at transcriptional and post-transcriptional levels, which is associated its RNA binding ability in HUVECs. The discovery extends our understanding on the functions and molecular mechanisms of galectin-1 during the development of angiogenesis, which could be served as a therapeutic option in anti-angiogenic treatment in future.
2022-12-23 | GSE201537 | GEO
Project description:Galectin-1-RNA interaction map reveals its novel regulatory roles in angiogenesis
| PRJNA615386 | ENA
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:Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice
| PRJNA561718 | ENA