MiR-29a regulates liver fibrosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67423 | GEO | 2015/03/31
SECONDARY ACCESSION(S): PRJNA279864
REPOSITORIES: GEO
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Project description:To confirm the mechanism of miR-29a in liver fibrosis healing, we have employed whole genome microarray expression profiling as a discovery platform to identify genes. CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been observed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis. We can get only one gene (PDGF-c) as a target of miR-29a which relate to liver fibrosis and down-regulated more than 1.5 times in common miR-29a injected group than N.C group. CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been obserbed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis.
2015-03-31 | E-GEOD-67423 | biostudies-arrayexpress
Project description:Abstract from Knabel et al. PLoS One (2015): Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include mir29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-β. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of mir-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders. The Taqman MicroRNA Array (Taqman Array Rodent MicroRNA A Cards v2.0, ABI) was run, using manufacturer's protocols, on 3 groups of mice with varying amounts fibrotic injury. The groups include carbon tetrachloride intraperitinially injected bi-weekly for 1, 4, and 8 weeks with n=4, 3, and 2 respectively for each group. The RNA was isolated from whole liver using the MiRvana miRNA Isolation Kit (Ambion) according to manufacturer's protocols. The fold_change.txt contains the following data columns; ID_Ref: mmu-miR being quantified not-treated (FC): Fold Change compared to not-treated group using Geometric mean normalization 1 week (FC): Fold Change compared to not-treated group using Geometric mean normalization 4 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization 8 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization
2015-02-25 | E-GEOD-66278 | biostudies-arrayexpress
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218574 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218579 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218578 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218577 | GEO
Project description:RNAseq was applied to define the transcriptome of primary LSECs from rats with acute liver injury, mild liver fibrosis and advanced chronic liver disease (CLD) (due to CCl4 or thioacetamide administration). Results showed different transcriptomic profile during progression of CLD, and a large number of significant de-regulated genes (1412) were shared in cirrhotic CCl4- and TAA-LSECs (fold-change>1.5 and p-vale<0.05)compared with their respective healthy-LSECs.
2021-09-24 | GSE164878 | GEO
Project description:Abstract from Knabel et al. PLoS One (2015): Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include mir29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-β. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of mir-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders.
2015-02-25 | GSE66278 | GEO
Project description:Liver fibrosis is a common pathological process of various chronic liver diseases that can develop into liver cancer. MicroRNAs (miRNAs) are a king of non-coding RNA which are closely related to liver diseases. Thus, this research hope to explore the effect of miR-484 on liver fibrosis and reveal its mechanism. The miRNAs profiles were screened by microRNA sequencing and the location of miR-484 was identified by fluorescence in situ hybridization (FISH) in human liver fibrotic tissues. MiR-484 expression was detected by qRT-PCR in rat primary hepatic stellate cells (HSCs). Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the target gene of miR-484. Liver fibrosis specific signatures were analyzed by qRT-PCR and western blot after miR-484 mimic/inhibitor transfection. The cell apoptosis was detected by Annexin V-FITC/PI double staining. The effect of miR-484 silencing on fibrosis in vivo was investigated in thioacetamide (TAA) induced mice model using the adeno-associated virus carrying miR-484 inhibitor. Enrichment of miR-484 was observed in human liver fibrosis tissues and activated rat primary HSCs. FISH showed that miR-484 was prominently located at fibrotic region and the cytoplasm of HSCs in human liver tissues. Dual-luciferase reporter assay verified that the homeodomain-interacting protein kinases 1 (HIPK1) was the direct target of miR-484. After transfecting miR-484 inhibitor into HSC-T6, HIPK1 were significantly up-regulated, and α-SMA, col1a1, Wnt-3a, Wnt-5a, β-catenin and p-β-catenin were down-regulated, suggesting the restrain effect of miR-484 knockdown on HSCs activation. Conversely, the results were opposite with miR-484 mimic transfection. In addition, the apoptosis of HSC-T6 altered significantly after miR-484 modulation. Moreover, adeno-associated virus carrying miR-484 inhibitor alleviated mice liver fibrosis induced by TAA. In conclusion, miR-484 knockdown ameliorates liver fibrosis by promoting the apoptosis and suppressing HSCs activation via blocking Wnt/β-catenin signaling pathway. MiR-484 and its downstream gene HIPK1 might be selected as novel therapeutic targets of liver fibrosis.
2021-12-09 | GSE190366 | GEO