Summary of Study ST001856

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 PR001170. The data can be accessed directly via it's Project DOI: 10.21228/M8G98C This work is supported by NIH grant, U2C- DK119886.

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Study IDST001856
Study TitleThe metabolomic resetting effect of FG4592 in AKI to CKD transition (Part 2)
Study SummaryC57BL/6 mice were anesthetized using isoflurane. UIR was induced by clamping the right renal pedicle for 45 minutes and then releasing it to allow reperfusion, leaving the left kidney intact. Sham treated mice served as controls. Each mouse was located supine on a thermostatic pad (37 °C) to maintain its body temperature throughout the whole process. After 3 days of recovery, the mice received a daily intraperitoneal (i.p.) injection of FG4592 (10 mg/kg) or vehicle for 7 consecutive days. After treatment, the mice were sacrificed.Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 10 after UIR.
Institute
Children's Hospital of Nanjing Medical University
Last NameWeiyi
First NameChen
Address72 Guangzhou Road, Nanjing 210008, P. R. of China
Emailchen.weiyi@qq.com
Phone+862583117309
Submit Date2021-07-01
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-07-07
Release Version1
Chen Weiyi Chen Weiyi
https://dx.doi.org/10.21228/M8G98C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001170
Project DOI:doi: 10.21228/M8G98C
Project Title:Anti-anemia drug FG4592 retards the AKI to CKD transition by improving vascular regeneration and anti-oxidative capability
Project Type:MS analysis
Project Summary:Acute kidney injury (AKI) is a known risk factor for the development of chronic kidney disease (CKD), with no satisfactory strategy to prevent the progression of AKI to CKD. Damage to the renal vascular system and subsequent hypoxia are common contributors to both AKI and CKD. Hypoxia inducible factor (HIF) is reported to protect the kidney from acute ischemic damage and a novel HIF stabilizer, FG4592 (Roxadustat), has become available in the clinic as an anti-anemia drug. However, the role of FG4592 in the AKI-to-CKD transition remains elusive. In the present study, we investigated the role of FG4592 in the AKI-to-CKD transition induced by unilateral kidney ischemia-reperfusion (UIR). The results showed that FG4592, given to mice 3 days after UIR, markedly alleviated kidney fibrosis and enhanced renal vascular regeneration, possibly via activating the HIF-1α/vascular endothelial growth factor A (VEGFA)/VEGF receptor 1 (VEGFR1) signaling pathway and driving the expression of the endogenous antioxidant superoxide dismutase 2 (SOD2). In accordance with the improved renal vascular regeneration and redox balance, the metabolic disorders of the UIR mice kidneys were also attenuated by treatment with FG4592. However, the inflammatory response in the UIR kidneys was not affected significantly by FG-4592. Importantly, in the kidneys of CKD patients, we also observed enhanced HIF-1α expression which was positively correlated with the renal levels of VEGFA and SOD2. Together, these findings demonstrated the therapeutic effect of the anti-anemia drug FG-4592 in preventing the AKI-to-CKD transition related to ischemia and the redox imbalance.
Institute:Children's Hospital of Nanjing Medical University
Last Name:Weiyi
First Name:Chen
Address:72 Guangzhou Road, Nanjing 210008, P. R. of China
Email:chen.weiyi@qq.com
Phone:0086-25-8311-7309

Subject:

Subject ID:SU001933
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6
Age Or Age Range:8 weeks
Weight Or Weight Range:20-25 g
Gender:Male
Animal Animal Supplier:Model Animal Research Center of Nanjing University
Animal Housing:Standard specific pathogen free (SPF) conditions
Animal Light Cycle:12:12-h light/dark cycle
Animal Feed:food freely
Animal Water:water freely

Factors:

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

mb_sample_id local_sample_id surgery FG-4592(10 mg/kg)
SA174238a2sham -
SA174239a1sham -
SA174240a3sham -
SA174241a4sham -
SA174230a6UIR -
SA174231a8UIR -
SA174232a5UIR -
SA174233a7UIR -
SA174234a11UIR 10
SA174235a12UIR 10
SA174236a10UIR 10
SA174237a9UIR 10
Showing results 1 to 12 of 12

Collection:

Collection ID:CO001926
Collection Summary:Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 10 after UIR.
Sample Type:Kidney

Treatment:

Treatment ID:TR001945
Treatment Summary:C57BL/6 mice were anesthetized using isoflurane. UIR was induced by clamping the right renal pedicle for 45 minutes and then releasing it to allow reperfusion, leaving the left kidney intact. Sham treated mice served as controls. Each mouse was located supine on a thermostatic pad (37 °C) to maintain its body temperature throughout the whole process. After 3 days of recovery, the mice received a daily intraperitoneal (i.p.) injection of FG4592 (10 mg/kg) or vehicle for 7 consecutive days. After treatment, the mice were sacrificed. Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 10 after UIR.
Treatment Compound:FG4592
Treatment Dosevolume:10 mg/kg

Sample Preparation:

Sampleprep ID:SP001939
Sampleprep Summary:20 mg of each tissue sample were homogenized with 0.6 mL of 2 chlorophenylalanine (4 ppm) containing methanol (−20 °C), centrifuged, and filtered through a 0.22-μm membrane.

Combined analysis:

Analysis ID AN003008 AN003009
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Ultimate 3000 system Thermo Ultimate 3000 system
Column ACQUITY UPLC® HSS T3 column ACQUITY UPLC® HSS T3 column
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units AUC AUC

Chromatography:

Chromatography ID:CH002230
Chromatography Summary:A 2 μL aliquot of the samples was injected into a Thermo Ultimate 3000 system equipped with an ACQUITY UPLC® HSS T3 column (150 × 2.1 mm, 1.8 μm, Waters, Milford, MA, USA) maintained at 40 °C. The mobile phase for positive mode analysis consists of 0.1% formic acid in water (phase C) and 0.1% formic acid in acetonitrile (phase D), while the mobile phase for negative mode analysis consists of 5 mM ammonium formate in water (phase A) and acetonitrile (phase B). Phase C and D, as well as phase A and B, were mixed and delivered at a flow rate of 0.25 mL/min with a gradient program as follows: 0~1 min; 2% B/D; 1~9 min, 2%~50% B/D; 9~12 min, 50%~98% B/D; 12~13.5 min, 98% B/D; 13.5~14 min, 98%~2% B/D; 14~20 min, 2% D-positive model (14~17 min, 2% B-negative model).
Instrument Name:Thermo Ultimate 3000 system
Column Name:ACQUITY UPLC® HSS T3 column
Chromatography Type:Reversed phase

MS:

MS ID:MS002797
Analysis ID:AN003008
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proteowizard software (v3.0.8789)
Ion Mode:POSITIVE
  
MS ID:MS002798
Analysis ID:AN003009
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proteowizard software (v3.0.8789)
Ion Mode:NEGATIVE
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