Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

ABSTRACT: Increasing evidence has revealed a close relationship between circular RNAs (circRNAs) and the regulatory process of cell aging. Exploring the role and mechanism of circRNAs in cellular senescence may help to identify new anti-aging therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_012707 in renal aging.High-throughput sequencing was performed to detect the differential expression of circRNAs in kidney tissues of the old and young groups. qRT-PCR confirmed that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. SA-β-Gal, Masson Assay is used to evaluate the role of hsa_circ_0127071 in the aging process of kidney tissue.Using RIP, RNA pull down, and WB to study the interaction between hsa_circ_0127071 and aging related pathway proteins.In this study, we found that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. The activity of JAK2/STAT5 signaling pathway was decreased after silencing EIF4A3, which could delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by EPO processing, and the senescence of HGMCs increased. After treatment with LOS, the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings showed that hsa_circ_0127071 promoted renal aging, and confirmed the regulatory role of EIF4A3/hsa_circ_0127071/JAK2/STAT5 in the regulation of renal aging, providing a new therapeutic target for drug design and early diagnosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245017 | GEO | 2024/12/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Renal aging resembles a continuum between normal and diseased kidneys that potentiates inflammatory response to injury [diet]

Project description:Kidney aging is an irreversible physiological process and some suggest that kidney aging is viewed as a pathological condition. To enhance understanding of the molecular nature of renal aging, we performed whole kidney RNA sequencing in young mice (2-month-old) fed with standard diet versus those with adenine-enriched diet, and this bulk transcriptome was then compared with transcriptional changes with aging.

2020-12-31 | GSE148605 | GEO

YOD1 promotes renal fibrosis by stabilizing JAK2 through deubiquitination

Project description:Renal fibrosis is an important pathological change in the development of progressive kidney diseases. Ubiquitination is a post-translational modification of proteins involved in the regulation of various pathophysiological processes. In this study, we found that the deubiquitinating enzyme YOD1 is significantly upregulated in the kidney tissues of Ang II-challenged mice and Ang II upregulates YOD1 expression in renal tubular epithelial cells. YOD1 deficiency significantly alleviated renal injury and fibrosis induced by Ang II infusion in mice. Mechanistically, RNA-seq and co-immunoprecipitation analysis showed a pro-fibrotic protein, JAK2, as a YOD1-binding protein. We identify that JAK2 interacts with the C-terminal Znf domain of YOD1. YOD1 removed K48-linked ubiquitination of JAK2 at residue K970 via its active site C155, which stabilizes JAK2 and then maintains JAK2/STAT3 signaling pathway activation to induce pro-fibrotic gene expression in renal tubular epithelial cells. JAK2 inhibitors reversed the renal fibrosis promoted by YOD1 in mice. We also show increased levels of YOD1 and JAK2 in the kidney tissues of patients with renal fibrosis. In addition, YOD1 knockout significantly prevents unilateral ureteral ligation (UUO)-induced renal fibrosis in mice. Collectively, these findings identify YOD1 as a novel regulator in renal fibrosis via deubiquitinating JAK2.

2024-01-06 | GSE234355 | GEO

The comparison of MicroRNA profile of the dermis between young and old human

Project description:Skin aging is a process of structural and compositional remolding that can be manifested as wrinkling and sagging. Remarkably, the dermis plays a dominant role in the process of skin aging. Recent studies suggest that microRNAs (miRNAs) may play a role in the regulation of gene expression in organism aging. However, studies about age-related miRNAs in human skin remain limited. In order to obtain an overall view of miRNAs expression in human aged dermis, we have investigated the alteration of microRNAs during aging by examining biopsies of human dermis from 12 young and aged donors, and demonstrated that numerous microRNAs showed significant alteration in dermis tissue. Normal human dermal tissue from 12 consenting individuals. Old group vs young group. Old group: with the age over 60 years old; young group: with the age below 10 years old; each group was constituted of 6 individuals.

2016-02-05 | E-GEOD-72264 | biostudies-arrayexpress

EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

Project description:EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

| PRJNA1026625 | ENA

RNA Sequencing and Bioinformatics Analysis of CircRNAs in Asphyxial Newborns with Acute Kidney Injury

Project description:Objective: As one kind of novel non-coding RNA with high stability and conservatism, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidence has supported the important role of circRNAs in renal diseases, the specific mechanism still remains unknown in neonatal acute kidney injury (AKI). Methods: High throughput sequencing analysis was applied to investigate the expression patterns of circRNAs in the comparison between hypoxia induced AKI neonates and controls. Then, bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs and construct the network of circRNA-miRNA interaction. Results: (1) We identified 296 differentially expressed circRNAs (circRNAs with Fold change > 2 and P value < 0.05). Of them, 184 circRNAs were markedly up-regulated and 112 were significantly down-regulated in the AKI group. (2) Bioinformatics analysis indicated that the parental genes of the differentially expressed circRNAs were predominantly implicated in the cell and cell part, cellular process and cancer pathways. Conclusion: This study could contribute to future research of circRNAs in the pathogenesis of neonatal AKI and facilitate the identification of novel therapeutic targets of circRNAs.

2023-01-11 | GSE222578 | GEO

A systems approach identifies progeroid Ercc1[-/Δ] mice as a model system for kidney aging.

Project description:Using these samples, it has been shown that the transcriptional landscape in glomeruli of Ercc1[-/Δ] mice at a rather young age of 14 weeks mimics that of mice which have undergone real-life renal aging. Thus, young Ercc1[-/Δ] mice can be used as a model system for glomerular aging in future studies. The RNAs origin from glomerular tissues of mice of 2 distinct genotypes at 3 distinct stages of age. Between 3 and 6 replicates have been prepared per group.

2012-12-21 | E-GEOD-43061 | biostudies-arrayexpress

Effect of perinatal obesity on premature kidney aging signaling

Project description:Chronic Kidney Disease (CKD), a global health burden, is strongly associated with age-related renal function decline, hypertension and diabetes, frequent consequences of obesity. Despite extensive studies the mechanisms determining susceptibility to CKD remain elusive. Clinical evidence together with prior studies from our group showed that perinatal metabolic disorders after maternal obesity adversely affect kidney structure and function throughout life. Since obesity and aging processes converge in similar pathways we tested if perinatal obesity induced by High-Fat Diet (HFD)-fed female mice sensitizes aging-associated mechanism in kidneys of newborn mice. Tissue from the kidney cortex and the kidney medulla was collected from offspring of control or HFD-fed mice.

2022-12-31 | E-MTAB-10954 | biostudies-arrayexpress

Hepatic Deletion of Janus Kinase 2 Counteracts Inflammation, Oxidative Stress and Liver Cancer Formation in Growth Hormone Transgenic Mice

Project description:Impairment of hepatic growth hormone (GH)- janus kinase (JAK) 2- signal transducer and activator of transcription (STAT) 5 signaling is associated with non-alcoholic fatty liver disease, while persistently high levels of GH can result in hepatic inflammation and liver cancer. Despite its anti-steatotic functions, STAT5 in hepatocytes has been implicated to be a tumor suppressor, whose loss strongly accelerates tumor formation in the presence of high GH levels. Yet, it remains unclear whether the upstream kinase JAK2 exerts similar tumor-suppressive functions. To address this question, we crossed a mouse model of inflammatory liver cancer (GHtg) to mice harboring the hepatocyte-specific deletion of JAK2 (JAK2Îhep) and compared them to GHtgSTAT5Îhep mice. We show that JAK2 deficiency in the GHtg background resulted in profound steatosis at young age due to ectopic lipid redistribution and increased hepatic de novo lipogenesis. Generation of reactive oxygen species (ROS) was increased in all genotypes compared to wildtype controls, while DNA damage and lipid peroxidation were observed only in GHtg and GHtgSTAT5Îhep animals. Importantly, Affymetrix analysis revealed that the expression of glutathione S-transferases (GSTs), a major group of detoxification enzymes, was strongly upregulated in JAK2 deficient livers. In vitro and in vivo studies further confirmed that ruxolitinib-mediated inhibition of JAK2 led to significant upregulation of GSTs, indicating a direct involvement of JAK2 in the negative regulation of these genes. Strikingly, despite equally profound hepatosteatosis and ROS production as in GHtgSTAT5Îhep mice, loss of JAK2 significantly delayed tumor formation in GHtg mice. Conclusion: Thus, in absence of hepatic JAK2, mice were protected against elevated ROS-induced DNA damage and lipid peroxidation through significant expression of GSTs.

2016-10-01 | E-MTAB-3774 | biostudies-arrayexpress

Mitochondrial Calcium Uniporter Promotes Kidney Aging through Inducing Mitochondrial Calcium-Mediated Renal Tubular Cell Senescence

Project description:Kidney is a vital organ responsible for homeostasis in the body. To retard kidney aging is of great importance for maintaining body health. Whereas the therapeutic strategies targeting against kidney aging are not elucidated. Recent studies show mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, however, the underlying mechanisms of mitochondrial dysfunction in kidney aging have not been demonstrated. Herein, we found calcium overload, and the mitochondrial calcium uniporter (MCU) was induced in renal tubular cells and aged kidney. To activate MCU not only triggered mitochondrial calcium overload, but also induced reactive oxygen species (ROS) production and cellular senescence and age-related kidney fibrosis. Inversely, to block MCU or chelate calcium diminished ROS generation, restored mitochondrial homeostasis, and retarded cell senescence and protected against kidney aging. These results demonstrate MCU plays a key role in promote renal tubular cell senescence, which provides a new insight on the therapeutic strategy for fighting against kidney aging.

2024-10-02 | GSE262514 | GEO

Liver gene expression in animals with hepatocyte-specific deletion of JAK2

Project description:Growth hormone signaling in hepatocytes is fundamentally important. Disruptions in this pathway have led to fatty liver and other metabolic abnormalities. Growth hormone signals through the JAK2/STAT5 pathway. Mice with hepatocyte specific deletion of STAT5 were previously shown to develop fatty liver. Our aim in this study was to determine the effect of deleting JAK2 in hepatocytes on liver gene expression. To do so, we generated animals with hepatocyte specific deletion of JAK2. Hepatocyte-specific JAK2-deficient mice (JAK2L) were generated by mating floxed JAK2 mice (in a mixed (C57Bl/6:129Sv) background) to mice carrying an Alb promoter-regulated Cre transgene on a 100% C57Bl/6 background purchased from the Jackson Labs. Livers were harvested from 8 week old animals for RNA extraction and hybridization.

2011-04-30 | E-GEOD-26188 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data