Summary of project PR001585

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001585. The data can be accessed directly via it's Project DOI: 10.21228/M8TD8H This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001585
Project DOI:doi: 10.21228/M8TD8H
Project Title:Mouse kidney metabolomic studies
Project Type:MS quantitative analysis
Project Summary:Chronic kidney disease secondary to cystic kidney disease is a leading cause of mortality in patients with tuberous sclerosis complex (TSC) disease. The mechanisms underlying TSC cystic kidney disease are obscure, with no interventions available to prevent cyst formation. Here, we reveal for the first time the misregulated metabolic pathways in TSC kidneys and their relevance to TSC-associated cytogenesis. To this end, we have analyzed the metabolic profile of the whole kidney as well as sorted proximal tubule cell (PTCs) extracts. The metabolomics data show that Tsc1 deletion in nephron progenitor cells changes the arginine biosynthesis pathway as well as a substantial number of metabolic pathways. These changes were associated with overexpression of argininosuccinate synthetase 1 (ASS1), a rate-limiting enzyme in the arginine biosynthetic pathway in TSC KO mice and human kidneys. The rise in ASS1 expression is dependent on mTORC1 activity. Arginine depletion in vitro and in vivo prevented the rise in mTORC1 activity and cell cycle progression and averted the overexpression of previously described cytogenetic signaling proteins, including c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduced the TSC cystic load, indicating the potential therapeutic effects of arginine deprivation as a treatment of TSC-associated kidney disease.
Institute:Hadassah Medical Center
Department:Pediatric Nephrology
Laboratory:Wohl Institute for Translational Medicine
Last Name:Ben-Dov
First Name:Iddo
Address:Ein Karem Campus, Jerusalem, NA, 9211001, Israel
Funding Source:This work was supported by grants from the Israel Science Foundation (MN 2030/21 and OV 2358/18), the TSC alliance research grant (OV), the research authority of Hadassah Hebrew University Medical Center (OV). OV and MN are Wohl’s Translation Research Institute research associates at Hadassah-Hebrew University Medical Center
Contributors:Athar Amleh, Lana Watad, Ifat Abramovich, Bella Agranovich, Eyal Gottlieb, Iddo Z. Ben-Dov, Morris Nechama and Oded Volovelsky

Summary of all studies in project PR001585

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002457 Mouse kidney metabolomics (Whole kidney) Mus musculus Hadassah Medical Center MS 2023-02-26 1 26 Uploaded data (1.3G)*
ST002458 Mouse kidney metabolomics (Proximal tubular cells) Mus musculus Hadassah Medical Center MS 2023-02-26 1 9 Uploaded data (401M)*