Summary of Study ST001855
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001855 |
| Study Title | The metabolomic resetting effect of FG4592 in AKI to CKD transition (Part 1) |
| Study 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 18 consecutive days. After treatment, the mice were sacrificed. Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 21 after UIR. |
| Institute | Children's Hospital of Nanjing Medical University |
| Last Name | Chen |
| First Name | Weiyi |
| Address | 72 Guangzhou Road, Nanjing 210008, P. R. of China |
| chen.weiyi@qq.com | |
| Phone | 0086-25-8311-7309 |
| Submit Date | 2021-06-30 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-07-07 |
| Release Version | 1 |
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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: | SU001932 |
| 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) |
|---|---|---|---|
| SA174226 | b2 | sham | - |
| SA174227 | b1 | sham | - |
| SA174228 | b3 | sham | - |
| SA174229 | b4 | sham | - |
| SA174218 | b6 | UIR | - |
| SA174219 | b8 | UIR | - |
| SA174220 | b5 | UIR | - |
| SA174221 | b7 | UIR | - |
| SA174222 | b11 | UIR | 10 |
| SA174223 | b12 | UIR | 10 |
| SA174224 | b10 | UIR | 10 |
| SA174225 | b9 | UIR | 10 |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO001925 |
| Collection Summary: | Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 21 after UIR. |
| Sample Type: | Kidney |
Treatment:
| Treatment ID: | TR001944 |
| 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 18 consecutive days. After treatment, the mice were sacrificed. Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 21 after UIR. |
| Treatment Compound: | FG4592 |
| Treatment Dose: | 10 mg/kg |
Sample Preparation:
| Sampleprep ID: | SP001938 |
| Sampleprep Summary: | 20 mg of each tissue sample were homogenized with 0.6 mL of 2 chloro phenylalanine (4 ppm) containing methanol (−20 °C), centrifuged, and filtered through a 0.22-μm membrane |
Combined analysis:
| Analysis ID | AN003006 | AN003007 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Thermo Ultimate 3000 system | Thermo Ultimate 3000 system |
| Column | Waters ACQUITY UPLC HSS T3 | Waters ACQUITY UPLC HSS T3 |
| 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: | CH002229 |
| 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: | Waters ACQUITY UPLC HSS T3 |
| Column Temperature: | 40 |
| Flow Gradient: | 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% A/B; 1-9 min, 2%-50% A/B; 9-12 min, 50%-98% A/B; 12-13.5 min, 98% A/B; 13.5-14 min, 98%-2% A/B; 14-20 min, 2% B-positive model (14-17 min, 2% B-negative model) |
| Flow Rate: | 0.25ml/min |
| Solvent A: | 100% water; 5mM ammonium formate |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS002795 |
| Analysis ID: | AN003006 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Proteowizard software (v3.0.8789) |
| Ion Mode: | POSITIVE |
| MS ID: | MS002796 |
| Analysis ID: | AN003007 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Proteowizard software (v3.0.8789) |
| Ion Mode: | NEGATIVE |
