Summary of Study ST003043

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001894. The data can be accessed directly via it's Project DOI: 10.21228/M8WQ6G This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003043
Study TitleRetinoic acid receptor alpha activity in proximal tubules prevents kidney injury and fibrosis
Study SummaryRetinoid levels of all-trans-retinol, retinoic acid, and retinyl palmitate were measured in the kidney and serum of GCERRARaD (kidney proximal tubule RARalpha knockout mice) females 3 days or 3 months post-tamoxifen (n=5/group) and age-matched Wild Type females (n=4).
Institute
Weill Cornell Medicine
Last NameTang
First NameXiao-Han
Address1300 York Ave, New York, NY10065
Emailxit2001@med.cornell.edu
Phone3478327329
Submit Date2024-01-14
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-01-18
Release Version1
Xiao-Han Tang Xiao-Han Tang
https://dx.doi.org/10.21228/M8WQ6G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001894
Project DOI:doi: 10.21228/M8WQ6G
Project Title:Retinoid levels measurement in kidney and serum
Project Type:MS analysis
Project Summary:Chronic kidney disease (CKD) is characterized by a gradual loss of kidney function and affects ca. 13.4% of the global population. Progressive tubulointerstitial fibrosis, driven in part by proximal tubule (PT) damage, is a hallmark of late stages of CKD and contributes to the development of kidney failure, for which there are limited treatment options. Normal kidney development requires signaling by vitamin A (retinol), which is metabolized to retinoic acid (RA), an endogenous agonist for the retinoic acid receptors (RAR alpha, beta, gamma). RARalpha levels are decreased in a mouse model of diabetic nephropathy (DN) and restored with RA administration; additionally, RA treatment reduces fibrosis. We developed a mouse model in which a spatiotemporal (tamoxifen-inducible) deletion of RARalpha in kidney PT cells of adult mice causes mitochondrial dysfunction, massive PT injury, and apoptosis without the use of additional nephrotoxic substances. Long-term effects (3-4.5 months) of RARalpha deletion include increased PT secretion of transforming growth factor beta (TGF-beta1), inflammation, interstitial fibrosis, and decreased kidney function, all of which are major features of human CKD. Therefore, RARalpha’s actions in proximal tubules (PTs) are crucial for PT homeostasis, and loss of RARalpha causes injury and a key CKD phenotype.
Institute:Weill Cornell Medicine
Last Name:Tang
First Name:Xiao-Han
Address:1300 Yates Avenue, New York, NY 10065
Email:xit2001@med.cornell.edu
Phone:3478327329
Publications:DiKun KM et al, RETINOIC ACID RECEPTOR a ACTIVITY IN PROXIMAL TUBULES PREVENTS KIDNEY INJURY AND FIBROSIS. PNAS, 2024.

Subject:

Subject ID:SU003158
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Treatment
SA330389Serum3DMP1positiveMutant tamoxifen, 3day
SA330390Serum3DMP2positiveMutant tamoxifen, 3day
SA330391Serum3DMP3positiveMutant tamoxifen, 3day
SA330392Kidney3DM1negativeMutant tamoxifen, 3day
SA330393Serum3DMN1negativeMutant tamoxifen, 3day
SA330394Serum3DMP5positiveMutant tamoxifen, 3day
SA330395Serum3DMN4negativeMutant tamoxifen, 3day
SA330396Serum3DMN3neagtiveMutant tamoxifen, 3day
SA330397Serum3DMN2negativeMutant tamoxifen, 3day
SA330398Serum3DMN5negativeMutant tamoxifen, 3day
SA330399Serum3DMP4positiveMutant tamoxifen, 3day
SA330400Kidney3DM2negativeMutant tamoxifen, 3day
SA330401Kidney3DM5negativeMutant tamoxifen, 3day
SA330402Kidney3DM4negativeMutant tamoxifen, 3day
SA330403Kidney3DM3negativeMutant tamoxifen, 3day
SA330404Serum3MMN3negativeMutant tamoxifen, 3month
SA330405Serum3MMN2negativeMutant tamoxifen, 3month
SA330406Serum3MMP5positiveMutant tamoxifen, 3month
SA330407Serum3MMP3positiveMutant tamoxifen, 3month
SA330408Serum3MMP2positiveMutant tamoxifen, 3month
SA330409Serum3MMP4positiveMutant tamoxifen, 3month
SA330410Serum3MMN5negativeMutant tamoxifen, 3month
SA330411Serum3MMN4negativeMutant tamoxifen, 3month
SA330412Serum3MMP1positiveMutant tamoxifen, 3month
SA330413Serum3MMN1negativeMutant tamoxifen, 3month
SA330414Kidney3MM4negativeMutant tamoxifen, 3month
SA330415Kidney3MM2negativeMutant tamoxifen, 3month
SA330416Kidney3MM1negativeMutant tamoxifen, 3month
SA330417Kidney3MM5negativeMutant tamoxifen, 3month
SA330418Kidney3MM3negativeMutant tamoxifen, 3month
SA330419Serum3DWN2negativeWild_Type tamoxifen, 3day
SA330420Serum3DWP4positiveWild_Type tamoxifen, 3day
SA330421Serum3DWP3positiveWild_Type tamoxifen, 3day
SA330422Serum3DWN3negativeWild_Type tamoxifen, 3day
SA330423Kidney3DW4negativeWild_Type tamoxifen, 3day
SA330424Kidney3DW1negativeWild_Type tamoxifen, 3day
SA330425Kidney3DW2negativeWild_Type tamoxifen, 3day
SA330426Kidney3DW3negativeWild_Type tamoxifen, 3day
SA330427Serum3DWP1positiveWild_Type tamoxifen, 3day
SA330428Serum3DWP2positiveWild_Type tamoxifen, 3day
SA330429Serum3DWN4negativeWild_Type tamoxifen, 3day
SA330430Serum3DWN1negativeWild_Type tamoxifen, 3day
SA330431Serum3MWP1positiveWild_Type tamoxifen, 3month
SA330432Serum3MWP2positiveWild_Type tamoxifen, 3month
SA330433Serum3MWP4positiveWild_Type tamoxifen, 3month
SA330434Serum3MWN1negativeWild_Type tamoxifen, 3month
SA330435Serum3MWN2negativeWild_Type tamoxifen, 3month
SA330436Serum3MWP3positiveWild_Type tamoxifen, 3month
SA330437Serum3MWN4negativeWild_Type tamoxifen, 3month
SA330438Kidney3MW3negativeWild_Type tamoxifen, 3month
SA330439Kidney3MW4negativeWild_Type tamoxifen, 3month
SA330440Kidney3MW1negativeWild_Type tamoxifen, 3month
SA330441Kidney3MW2negativeWild_Type tamoxifen, 3month
SA330442Serum3MWN3negativeWild_Type tamoxifen, 3month
Showing results 1 to 54 of 54

Collection:

Collection ID:CO003151
Collection Summary:serum and kidney were obtained from GCERRARaD females 3 days or 3 months post-tam (n=5/group) and age-matched wild-type females (n=4)
Sample Type:Kidney; Serum

Treatment:

Treatment ID:TR003167
Treatment Summary:Mutant and wild-type female mice were treated with tamoxifen for 3 days or 3 months.

Sample Preparation:

Sampleprep ID:SP003164
Sampleprep Summary:To extract metabolites, frozen kidney cortices were weighed, and ca 20 mg of each cortex was added to a tube containing 650 μL of 80% methanol (diluted in dH2O). Sample tubes were placed in a bead homogenizer for 1 minute at a frequency of 30/s. Samples were then placed in a -20℃ freezer for 10 minutes, centrifuged for 10 minutes at 15,000 RPM in 4℃, and the supernatant was moved to a new tube. The remaining pellets were then re-extracted with 400 μL of 80% methanol, following the above procedure of homogenization and centrifugation. The supernatant was then added to the supernatant pool obtained from the first extraction. The pellet was re-extracted for a third time using 350 μL of 80% MeOH and supernatant was again added to the pool from the first two extractions. The supernatant pool was placed at -20℃ for 15 minutes, centrifuged for 20 minutes at 15,000 RPM, and transferred to a new tube. The methanolic extract samples were speed-vacuumed and reconstituted in 70% acetonitrile (diluted in dH2O) containing 0.025% acetic acid at a protein concentration of 3μg/μL. For serum preparation, samples were diluted 10-fold with 70% acetonitrile (diluted in dH2O) containing 0.025% acetic acid, and centrifuged for 20 minutes at 20,000 g.

Combined analysis:

Analysis ID AN004992
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1290 Infinity II
Column MicroSolv Cogent Diamond Hydride (150 × 2.1 mm, 4.0 um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6550 QTOF
Ion Mode UNSPECIFIED
Units abundance

Chromatography:

Chromatography ID:CH003771
Instrument Name:Agilent 1290 Infinity II
Column Name:MicroSolv Cogent Diamond Hydride (150 × 2.1 mm, 4.0 um)
Column Temperature:25
Flow Gradient:0-1 min, 99% B; 1-15 min, a linear gradient to 20% B; 15.1-29 min, 0% B; 29.1-37 min, 99% B
Flow Rate:0.4mL/min
Solvent A:6 uM edta and 0.025% acetic acid in isopropanol:H2O (50:50)
Solvent B:6 uM edta and 5mM ammonium acetate in CH3CN: H2O (90:10)
Chromatography Type:HILIC

MS:

MS ID:MS004732
Analysis ID:AN004992
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The serum samples have negative and positive mode data. The kidney samples have negative mode data. MassHunter B10 MassHunter B10 MassHunter Profinder (B10)
Ion Mode:UNSPECIFIED
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