Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Discovery of natural small-molecules to combat kidney fibrosis

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE243694 | GEO | 2023/10/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

2021-01-19 | PXD016447 | Pride

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [ChIP-Seq]

Project description:Renal fibrosis is a common pathological endpoint that is challenging to reverse in chronic kidney disease (CKD) independently of the underlying causes. Although myofibroblasts are mainly responsible for the accumulation of a fibrillar collagen-rich extracellular matrix (ECM), recent reports revealed their heterogeneity in proliferative and fibrotic activities, mirroring specific metabolic states that drive fibrosis. Here, we investigate the role of E3 ubiquitin-protein ligase WWP2 in the metabolic reprogramming of renal myofibroblasts in fibrosis. The tubulointerstitial expression of WWP2 contributes to the progression of fibrosis in CKD patients and in pre-clinical models of CKD. WWP2 deficiency leads to increased fatty acid oxidation, boosting mitochondrial respiration, promoting myofibroblast proliferation and arresting pro-fibrotic activation, thus ameliorating kidney fibrosis. Specifically, WWP2 suppresses the transcription of PGC-1α, which mediates the metabolic and proliferative changes in fibrotic myofibroblasts. Pharmacological intervention targeting PGC-1α reverses the pro-fibrotic effect of WWP2. These findings reveal a previously unappreciated WWP2-PGC-1α axis underlying the metabolic reprogramming of myofibroblasts during renal fibrosis, which could provide a new target for therapeutic intervention in CKD.

2024-05-19 | GSE267765 | GEO

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [bulk RNA-seq]

2024-02-05 | GSE241503 | GEO

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [scRNA-seq]

2024-02-05 | GSE241502 | GEO

Quantitative proteomic analysis of hypoxia induced primary kidney cells

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. Nevertheless, despite numerous research efforts, both the definitive mechanism underlying the progression from CKD to end stage renal disease and an effective treatment have remained elusive. In this study, We utilized TMT-multiplexed quantitative proteomics approaches to identify protein expression changes associated with chronic injury in primary cultured renal cells.

2021-01-19 | PXD019678 | Pride

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

Project description: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.

2023-01-30 | GSE178109 | 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

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

2013-02-10 | GSE38117 | 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

FERM domain protein 3 Kidney Biopsy

Project description:We examined the transcriptional profile of human kidney biopsies, aiming to provide insight into the mechanisms of progressive CKD. This approach led to the identification of FERM domain protein 3, (FRMD3) as a molecular driver of disease. Transcriptome profiling was performed in human renal biopsy tissue and correlated with parameters of kidney function, including estimated glomerular filtration rate (eGFR), degree of renal tubulointerstitial fibrosis (%TIF), as well as CKD progression over a median follow-up period of 60 months. Transcriptome analysis performed in two independent cohorts of patients with CKD (n=24 and n=17, respectively) identified a cluster of genes (n=93) significantly correlated (FDR P<0.05) with eGFR and %TIF, and associated with CKD progression, with enrichment for pathways associated with inflammation and immune-cell mediated infiltration. Expression of FRMD3, a previously reported candidate gene from human genetics studies in CKD, was negatively correlated with indices of CKD severity and progression. Knockdown of FRMD3 in human kidney epithelial cells enhanced fibrotic responses to the cytokine transforming growth factor-beta (TGF-β1). Analysis of FRMD3 binding partners indicated enrichment of proteins implicated in mitochondrial function and remodeling of epithelial adherens junctions. Lentivirus-mediated knockdown of FRMD3 in renal tubule epithelial cells yielded a significant reduction (>35%) in NAD(P)H-dependent oxidoreductase activity, and a corresponding increase in caspase activity (50%). Using global transcriptome profiling we define a cluster of transcripts associated with severity of CKD and identify loss of FRMD3 expression as a potential molecular driver. Loss of FRMD3 expression may contribute to mitochondrial function and TIF.

2024-11-06 | PXD015297 | Pride

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