Increased expression of yes-associated protein/YAP and transcriptional coactivator with PDZ-binding motif/TAZ activates intestinal fibroblasts to promote intestinal obstruction in Crohn’s disease
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ABSTRACT:
PROVIDER: PRJNA730016 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14540091_1.fastq.gz | Fastqsanger.gz | |||
| SRR14540091_2.fastq.gz | Fastqsanger.gz | |||
| SRR14540092_1.fastq.gz | Fastqsanger.gz | |||
| SRR14540092_2.fastq.gz | Fastqsanger.gz | |||
| SRR14540093_1.fastq.gz | Fastqsanger.gz |
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Project description:The results of this study indicate that the expression of YAP/TAZ was significantly upregulated in stenotic fibroblasts, which was associated with the YAP/TAZ target gene signature. YAP/TAZ knockdown suppressed the activation of intestinal fibroblasts. In intestinal fibroblasts, YAP/TAZ were activated by the Rho-ROCK1 signalling pathway. High YAP/TAZ expression was positively correlated with ROCK1 expression, which is a prognostic marker for intestinal obstruction in CD patients.
2021-07-02 | GSE174460 | GEO
Project description:In a rat model of induced intestinal obstruction, a transcriptomic analysis was used to measure global gene expression. Rat fetuses small intestines of different stages of development (ED15, ED17, ED19 and ED21, were studied as non-operated controls and compared to upper and lower segments of rat fetuses small intestine with an induced obstruction (ligature at ED18).
2017-10-16 | E-MTAB-5981 | biostudies-arrayexpress
Project description:BackgroundIntestinal obstruction caused by intestinal fibrosis is a common and serious complication of Crohn's disease (CD). Intestinal fibroblasts, the main effector cells mediating gastrointestinal fibrosis, are activated during chronic inflammation. However, the mechanism of fibroblast activation in CD has not been well elucidated.MethodsFibroblasts isolated from stenotic and nonstenotic intestines of CD patients were used for RNA sequencing. Immunohistochemical and immunofluorescent staining was performed to evaluate the correlation between intestinal fibrosis and YAP/TAZ expression in our CD cohort and a DSS-induced chronic colitis murine model. A Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) inhibitor was used to explore the ROCK1-YAP/TAZ axis in intestinal fibroblasts in vitro and DSS-induced chronic colitis murine model in vivo.FindingsThe expression of YAP/TAZ was significantly upregulated in stenotic fibroblasts, which was associated with the YAP/TAZ target gene signature. YAP/TAZ knockdown suppressed the activation of intestinal fibroblasts. In intestinal fibroblasts, YAP/TAZ were activated by the Rho-ROCK1 signalling pathway. High YAP/TAZ expression was positively correlated with ROCK1 expression, which is a prognostic marker for intestinal obstruction in CD patients.InterpretationYAP/TAZ activation can lead to fibroblast activation and intestinal obstruction in CD. The effect of ROCK1 inhibitor on alleviating intestinal fibrosis is associated with YAP/TAZ inhibition. Targeted inhibition of YAP/TAZ in fibroblasts may be a potential therapeutic strategy to suppress intestinal fibrosis in CD.FundingThis work was supported by the National Key R&D Program of China (2019YFC1316002), the NSFC (81873547, 82073201, 81874177, 82000481) and the Shanghai Sailing Program (20YF1429400).
| S-EPMC8243379 | biostudies-literature
Project description:Urethra was partially ligated and the urinary bladder was removed 10 days or 6 weeks after obstruction. Sham operated rats were used as controls. An addtitonal group of rats were repoerated 6 weeks after surgery and the obstruction was removed. These rats were then sacrificed 10 days after deobstruction. The bladder (including the urothelium) was frozen and used for RNA extraction. Urinary bladders from sham-operated, 10 days and 6 weeks after obstruction and rats 10 days after deobstruction were compared. mRNA and microRNA were both analyzed.
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Project description:Hepatocellular carcinoma (HCC) is a disease with high unmet medical need. Most patients are diagnosed at late stage with few therapeutic options and a dismal prognosis. While molecular genomic studies have been helpful in improving the understanding and treatment of many types of cancer, their impact on HCC has been negligible so far. This is largely due to a poor understanding of the underlying mechanisms of this cancer and the lack of dominant oncogene that can be targeted pharmacologically. Here we report the identification of a novel Yes oncogenic signaling pathway in HCC that has escaped large-scale molecular genetic studies. Using a combination of genetic and pharmacological interventions in cellular and mouse models of HCC, we show that Yes activity is necessary for HCC cell proliferation. Transgenic expression of activated Yes in mouse hepatocytes is sufficient to induce liver tumorigenesis. Mechanistically, we found that Yes directly phosphorylates YAP and TAZ, promoting their nuclear accumulation and transcriptional activity in HCC cells and liver tumors, and that YAP/TAZ are effectors of Yes oncogenic transformation. Src-family kinase activation correlates with YAP tyrosine phosphorylation and nuclear localization in human HCC, and is associated with increased tumor burden. Specifically, high Yes activity predicts significantly shorter overall survival in HCC patients. Our findings identify Yes as a potential therapeutic target in HCC.
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Project description:Hepatocellular carcinoma (HCC) is a disease with high unmet medical need. Most patients are diagnosed at late stage with few therapeutic options and a dismal prognosis. While molecular genomic studies have been helpful in improving the understanding and treatment of many types of cancer, their impact on HCC has been negligible so far. This is largely due to a poor understanding of the underlying mechanisms of this cancer and the lack of dominant oncogene that can be targeted pharmacologically. Here we report the identification of a novel Yes oncogenic signaling pathway in HCC that has escaped large-scale molecular genetic studies. Using a combination of genetic and pharmacological interventions in cellular and mouse models of HCC, we show that Yes activity is necessary for HCC cell proliferation. Transgenic expression of activated Yes in mouse hepatocytes is sufficient to induce liver tumorigenesis. Mechanistically, we found that Yes directly phosphorylates YAP and TAZ, promoting their nuclear accumulation and transcriptional activity in HCC cells and liver tumors, and that YAP/TAZ are effectors of Yes oncogenic transformation. Src-family kinase activation correlates with YAP tyrosine phosphorylation and nuclear localization in human HCC, and is associated with increased tumor burden. Specifically, high Yes activity predicts significantly shorter overall survival in HCC patients. Our findings identify Yes as a potential therapeutic target in HCC.
2022-01-05 | GSE179750 | GEO
Project description:Hepatocellular carcinoma (HCC) is a disease with high unmet medical need. Most patients are diagnosed at late stage with few therapeutic options and a dismal prognosis. While molecular genomic studies have been helpful in improving the understanding and treatment of many types of cancer, their impact on HCC has been negligible so far. This is largely due to a poor understanding of the underlying mechanisms of this cancer and the lack of dominant oncogene that can be targeted pharmacologically. Here we report the identification of a novel Yes oncogenic signaling pathway in HCC that has escaped large-scale molecular genetic studies. Using a combination of genetic and pharmacological interventions in cellular and mouse models of HCC, we show that Yes activity is necessary for HCC cell proliferation. Transgenic expression of activated Yes in mouse hepatocytes is sufficient to induce liver tumorigenesis. Mechanistically, we found that Yes directly phosphorylates YAP and TAZ, promoting their nuclear accumulation and transcriptional activity in HCC cells and liver tumors, and that YAP/TAZ are effectors of Yes oncogenic transformation. Src-family kinase activation correlates with YAP tyrosine phosphorylation and nuclear localization in human HCC, and is associated with increased tumor burden. Specifically, high Yes activity predicts significantly shorter overall survival in HCC patients. Our findings identify Yes as a potential therapeutic target in HCC.
2022-01-05 | GSE179749 | GEO
Project description:Hepatocellular carcinoma (HCC) is a disease with high unmet medical need. Most patients are diagnosed at late stage with few therapeutic options and a dismal prognosis. While molecular genomic studies have been helpful in improving the understanding and treatment of many types of cancer, their impact on HCC has been negligible so far. This is largely due to a poor understanding of the underlying mechanisms of this cancer and the lack of dominant oncogene that can be targeted pharmacologically. Here we report the identification of a novel Yes oncogenic signaling pathway in HCC that has escaped large-scale molecular genetic studies. Using a combination of genetic and pharmacological interventions in cellular and mouse models of HCC, we show that Yes activity is necessary for HCC cell proliferation. Transgenic expression of activated Yes in mouse hepatocytes is sufficient to induce liver tumorigenesis. Mechanistically, we found that Yes directly phosphorylates YAP and TAZ, promoting their nuclear accumulation and transcriptional activity in HCC cells and liver tumors, and that YAP/TAZ are effectors of Yes oncogenic transformation. Src-family kinase activation correlates with YAP tyrosine phosphorylation and nuclear localization in human HCC, and is associated with increased tumor burden. Specifically, high Yes activity predicts significantly shorter overall survival in HCC patients. Our findings identify Yes as a potential therapeutic target in HCC.
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Project description:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted. We performed unilateral ureteral obstruction of mice for 7 days, and harvested kidneys.
2012-12-05 | E-GEOD-42716 | biostudies-arrayexpress
Project description:To find miRNAs that involve in renal epithelial transition and renal fibrosis, we performed unilateral ureteral obstruction of mice for 7 days. After that, we harvested kidneys, and performed microarray of miRNA. Contralateral kidneys without ureteral obstruction were used as controls. miRNAs were purified from kidneys with ureteral obstruction and contralateral kidneys without ureteral obstruction. Then microarray of miRNA was performed (n=4). miRNAs up-regulated in kidneys with ureteral obsctruction compared with contralateral kidneys were sorted.
2012-12-05 | GSE42716 | GEO