Matches in SemOpenAlex for { <https://semopenalex.org/work/W4300690745> ?p ?o ?g. }
- W4300690745 abstract "ABSTRACT Nephron endowment is defined by fetal kidney growth and crucially dictates renal health in adults. Defects in the molecular regulation of nephron progenitors contribute to only a fraction of reduced nephron mass cases, suggesting alternative causative mechanisms. The importance of MAPK/ERK activation in nephron progenitor maintenance has been previously demonstrated, and here, we characterized the metabolic consequences of MAPK/ERK deficiency. Liquid chromatography/mass spectrometry-based metabolomics profiling identified 42 reduced metabolites, of which 26 were supported by in vivo transcriptional changes in MAPK/ERK-deficient nephron progenitors. Among these, mitochondria, ribosome and amino acid metabolism, together with diminished pyruvate and proline metabolism, were the most affected pathways. In vitro cultures of mouse kidneys demonstrated a dosage-specific function for pyruvate in controlling the shape of the ureteric bud tip, a regulatory niche for nephron progenitors. In vivo disruption of proline metabolism caused premature nephron progenitor exhaustion through their accelerated differentiation in pyrroline-5-carboxylate reductases 1 (Pycr1) and 2 (Pycr2) double-knockout kidneys. Pycr1/Pycr2-deficient progenitors showed normal cell survival, indicating no changes in cellular stress. Our results suggest that MAPK/ERK-dependent metabolism functionally participates in nephron progenitor maintenance by monitoring pyruvate and proline biogenesis in developing kidneys." @default.
- W4300690745 created "2022-10-04" @default.
- W4300690745 creator A5001272780 @default.
- W4300690745 creator A5005719054 @default.
- W4300690745 creator A5028639293 @default.
- W4300690745 creator A5028979905 @default.
- W4300690745 creator A5035455769 @default.
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- W4300690745 creator A5081131359 @default.
- W4300690745 creator A5089925444 @default.
- W4300690745 creator A5090535135 @default.
- W4300690745 date "2022-10-01" @default.
- W4300690745 modified "2023-10-14" @default.
- W4300690745 title "Omics profiling identifies the regulatory functions of the MAPK/ERK pathway in nephron progenitor metabolism" @default.
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