β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis
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PROVIDER: PRJNA795662 | ENA |
REPOSITORIES: ENA
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Project description:Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD) and renal fibrosis, suggesting intimate communication between the two diseases. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that tubular cell-derived exosomes were aroused by β-catenin in kidney fibrogenesis. Osteopontin (OPN), especially its N-terminal fragments (N-OPN), was encapsulated in β-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β-catenin in tubular cells (Ksp-β-catenin−/−) or gene ablation of CD44 (CD44−/−) greatly ameliorated renal fibrosis. Notably, N-OPN was secreted by exosome into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β-catenin.
2022-05-20 | PXD030696 | Pride
Project description:Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD) and renal fibrosis, suggesting intimate communication between the two diseases. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that tubular cell-derived exosomes were aroused by β-catenin in kidney fibrogenesis. Osteopontin (OPN), especially its N-terminal fragments (N-OPN), was encapsulated in β-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β-catenin in tubular cells (Ksp-β-catenin−/−) or gene ablation of CD44 (CD44−/−) greatly ameliorated renal fibrosis. Notably, N-OPN was secreted by exosome into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β-catenin.
2022-12-20 | GSE193282 | GEO
Project description:Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD), suggesting intimate communication between the two types of cells. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that exosomes were aroused by β-catenin in renal tubular cells. Osteopontin (OPN), especially its N-terminal fragment (N-OPN), was encapsulated in β-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β-catenin in tubular cells (Ksp-β-catenin-/- ) or gene ablation of CD44 (CD44-/- ) greatly ameliorated renal fibrosis. Notably, N-OPN was carried by exosome and secreted into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β-catenin.
| S-EPMC8936047 | biostudies-literature
Project description:Two orthotopic pancreatic tumor mouse models were used for ChIP-Seq and RNA-Seq to identify genome-wide dysfunction of H3K4me3 and gene expression. Mouse pancreatic tumors have a genome-wide increase in H3K4me3 deposition as compared to normal pancreas. Osteopontin (OPN) and its receptor CD44 were identified being up-regulated in pancreatic tumors by their promoter H3K4me3 deposition. OPN protein is increased in both tumor cells and tumor-infiltrating immune cells in human pancreatic carcinoma and is inversely correlated with pancreatic cancer patient survival. OPN is primarily expressed in tumor cells and monocytic myeloid-derived suppressor cells (M-MDSCs), whereas PD-L1 is expressed in tumor cells, M-MDSCs, polymorphonuclear MDSCs (PMN-MDSCs) and tumor-associated macrophages. WDR5 is essential for H3K4me3-specific histone methyltransferase activity and OPN expression in tumor cells and MDSCs. Pharmacological inhibition of WDR5 significantly decreased OPN protein level, suppressed pancreatic tumor growth, and significantly increased efficacy of anti-PD-1 immunotherapy in suppression of pancreatic tumor growth in vivo.
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Project description:To identify genes that are differentially expressed between CD44+ and CD44- cells in colonospheres, we have employed whole genome microarray expression profiling as a discovery platform. Colonospheres from four colon cancer patients were sorted into CD44+ and CD44- cells using the FACS Aria II Cell Sorter, and total RNA extracted from the cells were labeled with Cy3 and used for microarray analyses with Agilent Whole Human Genome Oligo Microarrays. Gene expression in fluorescence-activated cell-sorted CD44+ and CD44- cells derived from four colon cancer patients was measured.
2012-12-07 | E-GEOD-38706 | biostudies-arrayexpress
Project description:To investigate the significance of CD44+ hepatocellular carcinoma (HCC) HuH7 cells, gene expression profiles of CD44-positive HuH7, CD44-negative HuH7, and human nomal hepatocyes were analyzed. Results provide the insight into the significance of CD44-positive HCC cells as the liver CSCs.
2016-09-01 | GSE84223 | GEO
Project description:To investigate the significance of CD44+ hepatocellular carcinoma (HCC) HuH7 cells, microRNA (miRNA) expression profiles of CD44-positive HuH7, CD44-negative HuH7, and human nomal hepatocyes were analyzed. Results provide the insight into the significance of CD44-positive HCC cells as the liver CSCs.
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Project description:Gene expression profiling of CD44-CD133+ and CD44+CD133+ Caco2 population
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Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.
2020-06-01 | GSE148420 | GEO