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Analysis of proteome and phosphoproteome of mice kidney with deletion of renal tubular Raptor as compared to control animals

ABSTRACT: Raptor expression was specifically deleted in the tubular system of the kidney using an inducible Cre-Lox system under the control of a Pax8 promotor. Please see further details concerning the experimental procedures in the accompanied publication

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Kidney

DISEASE(S): Fanconi Syndrome

SUBMITTER: Markus Rinschen

LAB HEAD: Thomas Benzing

PROVIDER: PXD002422 | Pride | 2016-05-11

REPOSITORIES: Pride

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			Action	DRS
	20150410_RG_0089-150310MaRiTQS01.raw	Raw
	20150410_RG_0089-150310MaRiTQS02.raw	Raw
	20150410_RG_0089-150310MaRiTQS03.raw	Raw
	20150410_RG_0089-150310MaRiTQS04.raw	Raw
	20150410_RG_0089-150310MaRiTQS05.raw	Raw

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mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress

Project description:The mechanistic target of rapamycin mTORC1 is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTOR inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By utilizing constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in counter-current multiplication and urine concentration. Although mTORC2 partially compensated the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice, and caused pronounced apoptosis, diminished proliferation rates and delayed recovery. These findings identify mTORC1 as an essential regulator of tubular energy metabolism and as a crucial component of ischemic stress responses. Pharmacological inhibition of mTORC1 likely affects tubular homeostasis, and may be particularly deleterious if the kidney is exposed to acute injury. Furthermore, the combined inhibition of mTORC1 and mTORC2 may increase the susceptibility to renal damage. Raptor fl/fl*KspCre and Raptor fl/fl animals were sacrificed at P14 before the development of an overt functional phenotype. Kidneys were split in half and immediately snap frozen in liquid nitrogen.

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Targeted deletion of circadian clock gene Arntl in the nephron results in dysregulation of diverse metabolic pathways

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HEK-293T LC-MS/MS

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Project description:We investigated the role of mTORC1 in murine hematopoiesis by conditionally deleting the Raptor gene in murine hematopoietic stem cells. We observed mutliple alterations evoked by Raptor loss in hematopoiesis and profiled gene-expression alterations induced by raptor loss in Flt3-Lin-Sca1+cKit+ hematopoietic stem and progenitor enriched cell populations, 5 weeks post Raptor deletion. Flt3-Lin-Sca1+cKit+ cells were flow sorted from mice containing homozygous floxed alleles for exon 6 of the Raptor gene in the presence (MT group) or absence (WT group) of the MxCre transgene, which was induced with injections of mice with pIpC 5 weeks before cell isolation.

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