Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Indian Hedgehog release from inflamed epithelia links TNF-alpha to organ fibrosis

ABSTRACT: In chronic kidney disease (CKD) and with ageing, individuals lose regenerative capacity after renal injury and are predisposed to progressive fibrosis and cardiovascular disease. With ageing and CKD increased numbers of activated leukocytes are present in the circulation and within the kidney where they correlate with progressive fibrosis. The potential role of activated leukocytes in mediating progressive renal and systemic fibrosis remains incompletely understood. Here, we show that tumour necrosis factor alpha (TNFa) released with injury and aging promotes renal and cardiac fibrosis. We identify a Ubiquitin D expressing population of TNFa induced inflammatory proximal tubular epithelia (iPT) responsible for Indian Hedgehog release in aged and fibrotic kidneys. Indian Hedgehog production by iPT cells activates canonical Hedgehog signalling in Gli1+ stromal cells leading to activation, proliferation and fibrosis deposition. Our data links the immune activation seen in aging and chronic kidney disease to cardio-renal fibrosis. This provides multiple targets for antifibrotic therapies which we validate in murine models of aging and kidney disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE178109 | GEO | 2023/01/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Novel targets in renal fibrosis based on bioinformatic analysis II

Project description:Renal fibrosis is a widely used pathological indicator of progressive chronic kidney disease (CKD), and renal fibrosis mediates most progressive renal diseases as a final pathway. Nevertheless, the key genes related to the host response are still unclear. In this study, the potential gene network, signaling pathways, and key genes under UUO model in mouse kidneys were investigated by integrating two transcriptional data profiles.

2023-01-06 | GSE217654 | GEO

Novel targets in renal fibrosis based on bioinformatic analysis I

2023-01-06 | GSE217650 | GEO

Exploring new pathways involved during experimental renal fibrogenesis in the Unilateral Ureteral Obstruction

Project description:Chronic kidney disease (CKD) is a burden for Public Health and concerns millions of individuals worldwide. Independently of the cause, CKD is secondary to the replacement of functional renal tissue by extra-cellular matrix proteins (i.e fibrosis) that progressively impairs kidney function. The pathophysiological pathways that control the development of renal fibrosis are common to most of the nephropathies involving native kidneys or kidney grafts. Unfortunately, very few treatments are available to stop renal fibrosis and most of the therapeutic strategies are often barely able to slow down the progression of fibrogenesis in native kidneys. Therefore, it is mandatory to discover new therapeutic pathways to stop renal fibrosis. Our objective is to study new pathways involved in renal fibrosis. We thus decided to use the model of Unilateral Ureteral renal Obstruction in mice, a fast and reproducible experimental model of renal fibrosis. We studied renal fibrosis using experimental model of ureteral unilateral obstruction in mice, which was performed by complete ligation of the left ureter. The control lateral right kidney served as internal control.

2013-02-10 | E-GEOD-38117 | biostudies-arrayexpress

In-depth proteome profiling of kidney in 5/6 Nephrectomy rat model

Project description:Chronic kidney disease (CKD) is characterized by a slow and gradual loss of kidney function, with glomerular filtration loss over months or years, inevitably leading to end-stage renal disease. The renal failure resulting from this irreversible process derives from fibrotic lesions of each compartment of the kidney; glomerulosclerosis, vascular sclerosis, and tubulointerstitial fibrosis. Here, we aimed to specify CKD-related injury markers through proteomics analysis in animal kidney tissues.

2021-01-19 | PXD016447 | Pride

Exploring new pathways involved during experimental renal fibrogenesis in the Unilateral Ureteral Obstruction

2013-02-10 | GSE38117 | GEO

Discovery of natural small-molecules to combat kidney fibrosis

Project description:Chronic kidney disease (CKD) has become one of the greatest threats to public health, characterized by renal fibrosis. However, no treatment targeting renal fibrosis is available so far. Several natural diterpene compounds exhibit extraordinary inhibitory effects on TGF-β1-induced renal fibroblast activation and renal fibrosis in UUO mouse model. RNA-sequencing reveals the signaling pathways affected by these compounds. The direct target of the compounds are explored via quantitative mass spectrometry. Besides, the efficacies of the compounds are compared with pirfenidone, an FDA-approved drug for idiopathic pulmonary fibrosis, which is under clinical trials for treating CKD patients. Moreover, these compounds exhibit more potent anti-fibrotic activities than conventional CKD medications such as valsartan and enalapril. Taken together, our study discovered that these diterpeniods alleviate kidney fibrosis by blocking the pro-fibrotic signaling pathway, which has great potential for the treatment of CKD.

2023-10-20 | GSE243694 | GEO

β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis

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

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

Connectivity mapping of a chronic kidney disease progression signature identified lysine deacetylases as novel therapeutic targets

Project description:Motivation and design: Renal tubulointerstitial injury is an important determinant of chronic kidney disease (CKD) progression, yet treatment is limited to renin angiotensin system blockade. Accordingly, we performed global expression profiling in a 2 × 2 factorial design (N = 8 in each group) on RNA extracted from male Col4a3–/– mice and littermate controls on a 129X1/SvJ background at 4 and 7 weeks of age. Col4a3–/– mice have a mutation in the gene encoding the α3 chain of type IV collagen, associated with proteinuria and progressive loss of kidney function. We analyzed expression with Affymetrix GeneChip Mouse Gene 2.0 ST Arrays and derived a novel CKD progression signature based on aging and disease in Col4a3–/– mice. Using our progression signature, we sought to repurpose existing drugs for the treatment of progressive CKD. Results: Computational drug repurposing with the Connectivity Map identified lysine deacetylase inhibitor, vorinostat, as a novel candidate treatment for this murine model of CKD. Treatment with vorinostat attenuated tubulointerstitial injury, fibrosis, and altered inflammation. Vorinostat administration significantly increased the lifespan of Col4a3–/– mice although effects on urinary albumin excretion, plasma creatinine, and blood urea nitrogen were modest. Conclusions: Our data suggest that expression profiling and computational drug repurposing can be used to identify novel drugs that may reverse gene expression changes in experimental CKD. Lysine deacetylase inhibition may be a novel treatment approach to CKD associated with proteinuria and progressive tubulointerstitial injury.

2020-01-31 | GSE137086 | GEO

Development of gene expression profiles in human chronic kidney disease

Project description:A microarray analysis with renal biopsy specimens from CKD patients was conducted in order to identify the responsible genes associated with tubulointerstitial fibrosis and tubular cell injury in CKD. This study showed microarray profiles in total 53 biopsy specimens of CKD patients. In the discovery set, 554 down-regulated and 226 up-regulated signatures were identified. Then, the expressional changes of these genes were examined in the validation set. Gene expression profiles in human chronic kidney disease was explored using renal biopsy specimens. Two independent studies: discovery set and validation set were performed. This dataset is part of the TransQST collection.

2015-08-16 | E-GEOD-66494 | 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