Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Renal Proximal Tubule Cell-specific Megalin Deletion Induces Tubulointerstitial Nephritis in Mice Fed Western Diet

ABSTRACT: Pharmacological inhibition of megalin (also known as low-density lipoprotein receptor-related protein 2: LRP2) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), PTC-LRP2 +/+ and -/- littermates in an LDL receptor -/- background were generated and fed a Western diet to determine effects of PTC-derived megalin on atherosclerosis. PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor -/- mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 -/- mice fed the Western diet, but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 -/- mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not hypercholesterolemia. By contrast, female PTC-LRP2 -/- mice had no apparent renal pathologies. In vivo multiphoton microscopy demonstrated that PTC-specific megalin deletion dramatically diminished albumin accumulation in PTCs within 10 days of Western diet feeding. RNA sequencing analyses demonstrated the upregulation of inflammation-related pathways in kidney. Overall, PTC-specific megalin deletion leads to tubulointerstitial nephritis in mice fed Western diet, with severe pathologies in male mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE268879 | GEO | 2024/07/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Diet induced changes in mouse liver

Project description:Examination of gene expression profiles from liver of C57BL/6 mice and LDL receptor deficient mice fed on either a low fat diet or a high fat Western-style diet for 12 weeks. Three replicates of each condition analyzed. Keywords = LDL receptor deficiency, high fat diet, atherosclerosis, liver Keywords: repeat sample

2003-04-05 | GSE363 | GEO

Transcription profiling of livers of C57BL/6 mice and LDL receptor deficient mice fed on either low fat or high fat diet to study liver gene expression associated with diet.

2007-11-01 | E-GEOD-363 | biostudies-arrayexpress

Heterozygous midnolin knockout attenuates severity of nonalcoholic fatty liver disease in mice fed a Western-style diet high in fat, cholesterol, and fructose

Project description:We found that global heterozygous midnolin knockout attenuated the severity of nonalnonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose. This attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.

2023-05-03 | GSE226810 | GEO

Atlas of miRNome variations in different dyslipidemic conditions: a study in C57Bl/6, Ldlr-KO, and Pcsk9-KO mice.

Project description:In this study, mice with different genotypes and fed diets with different lipid content were enrolled, aiming to set up an atlas of miRNA expression levels in different organs with a relevant role in lipid/lipoprotein metabolism. Specifically, three genotypes were investigated: C57Bl/6 mice as controls, together with mice knock-out (KO) for LDLr (low-density lipoprotein receptor) and for PCSK9 (proprotein convertase subtilisin/kexin type 9). LDLr and PCSK9 are both involved in LDL turnover, the former mediating LDL clearance [PMID: 19299327], the latter causing the degradation of the LDLr protein [PMID: 17080197]. As a result, LDLrKO mice, because of their impaired LDL catabolism, are hypercholesterolemic and prone to atherosclerosis development, particularly when fed high-fat, cholesterol-containing diets [PMID: 8349823; PMID: 8182121]. On the contrary, PCSK9KO mice, characterized by an accelerated LDL catabolism, are hypocholesterolemic and atherosclerosis resistant [PMID: 15805190]. miRNA expression was investigated in liver, intestine, aorta, white adipose tissue and brain of mice on both standard and Western diet.

2023-09-06 | GSE227578 | GEO

Galnt11 differential tissue glycoproteomics

Project description:Chronic kidney disease (CKD) affects more than 20 million Americans and approximately 10% of the population worldwide, and thus represents a major public health concern. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise roles and mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of one GWAS identified gene by creating mice deficient for Galnt11, which encodes a member of the enzyme family that initiates protein Oglycosylation, an essential post-translational modification known to influence protein function and stability. We find that Galnt11-deficient mice display low molecular weight proteinuria and have specific defects in proximal tubule-mediated resorption of vitamin D binding protein, a1-microglobulin and retinol binding protein. Moreover, we identify the endocytic receptor megalin (LRP2) as a direct target of Galnt11 in vivo. Megalin in Galnt11-deficient mice displays reduced ligand binding and undergoes age-related loss within the kidney. Differential mass spectrometry revealed specific sites of Galnt11-mediated glycosylation within mouse kidney megalin/LRP2 that are known to be involved in ligand binding, suggesting that Oglycosylation directly influences the ability to bind ligands. In support of this, recombinant megalin containing these sites displayed reduced albumin binding in cells deficient for Galnt11. Our results provide insight into the association between GALNT11 and CKD, and identify a role for Galnt11 in proper kidney function.

2019-11-04 | PXD015429 | Pride

Transcription profiling of mouse C57BL/6 C3H/HeJ apoE-/- knockout aorta

Project description:Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit a marked difference in their susceptibility to atherosclerosis and the arterial wall has proven to be a source of the difference in atherosclerosis susceptibility. Genome-wide gene expression analysis was conducted in aortic walls of the two strains. Total RNA was extracted from aortas of 6-week-old female B6 and C3H apoE-deficient (apoE-/-) mice fed a chow or Western diet. 1514 genes in chow fed mice and 590 genes in Western fed mice were found to be differentially expressed between the two strains. RNA was extracted from aorta using a Trizol protocol. Total RNA was pooled in an equal amount from 4 mice for each group. Standard Affymetrix procedures were performed using 8ug of total RNA. Microarrays were used to detect gene expression in aortic walls of two apoE-deficient mouse strains when fed a chow or western diet. Experiment Overall Design: 4 groups of mice were studied: C57BL/6 apoE-/- mice on chow diet (03-62_BC), C57BL/6 apoE-/- mice on Western diet (03-62_BW), C3H/HeJ apoE-/- mice on chow diet (03-62_CC), and C3H/HeJ apoE-/- mice on Western diet (03-62_CW). Mice were weaned at 3 weeks of age onto a chow diet. At 4 weeks of age, mice were switched onto a western diet or continued the chow diet for 2 additional weeks.

2009-02-28 | E-GEOD-14854 | biostudies-arrayexpress

Cubilin-, Megalin- and Dab2-dependent transcription revealed by CRISPR/Cas9 knockout in kidney proximal tubule cells

Project description:The multiligand receptor megalin and its endocytic adaptor protein Dab2 play essential roles in maintaining the integrity of the apical endocytic pathway of proximal tubule cells, and have complex and poorly understood roles in the development of chronic kidney disease. Here we used RNASeq in CRISPR/Cas9 knockout technology in a well-differentiated cell culture model to identify PT-specific transcriptional changes that are directly consequent to the loss of megalin (Lrp2), cubilin (Cubn), or Dab2 (Dab2) expression.

2021-12-29 | GSE176090 | GEO

NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice

Project description:ApoE-/-mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE-/- mice to generate ApoE-/-NPRC-/- mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE-/-NPRC-/- versus ApoE-/- mice.

2023-07-04 | GSE233428 | GEO

D2Ome - rate constant estimation from heavy water metabolic labeling and LC-MS

Project description:We developed a software for extraction of protein decay rate constants from heavy water labeling followed by LC-MS experiments. We illustrate the program on application to normal diet and western diet fed LDLR-/- mice. We demonstrate that proteins subunits of 40S ribosomal complex have reduced stability in western diet fet mice.

2019-04-10 | PXD009493 | Pride

An Antagonist of Toll-like Receptor 7 and 9 lowers cholesterol and reduces atherosclerosis in hyperlipidemic mice

Project description:The impact of a dual TLR7 and TLR9 antagonist on hypercholesteremia and atherosclerosis was evaluated in hyperlipidemic mice. Treatment with antagonist induced a dose dependent reduction of total cholesterol (TC) and LDL-cholesterol. Changes in Adiponectin, Leptin and free fatty acids levels were observed. Plaque formation was inhibited in ApoE-/- and LDL-R-/- mice fed high fat diet and treated with the antagonist. Hepatic and renal steatosis was reduced by the treatment. Induction of IL-10 expression was inversely correlated with TC levels. The antagonist induced decrease in hepatic IKKα protein level and enhancement of Akt and Gsk3β phosphorylation. Treatment of C57BL/6 mice caused increase in hepatic LXR, PPARγ and ABCG1 expression and in stool content of TC. Antagonist treatment resulted in altered expression of several genes and pathways related to immune system, cholesterol, fatty acid and glucose metabolism. Data obtained suggest involvement of TLR7 and TLR9 in diet induced hyperlipidemia and atherosclerosis and demonstrate therapeutic potential of TLR7/9 antagonist.

2021-11-01 | GSE28125 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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