Integration of Epigenetic and Transcriptomic Signature reveals Key Transcription Factors involving in Renal Tubular Response to extracellular Stimuli
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ABSTRACT:
PROVIDER: PRJNA630979 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11728519_1.fastq.gz | Fastqsanger.gz | |||
| SRR11728519_2.fastq.gz | Fastqsanger.gz | |||
| SRR11728520_1.fastq.gz | Fastqsanger.gz | |||
| SRR11728520_2.fastq.gz | Fastqsanger.gz | |||
| SRR11728521_1.fastq.gz | Fastqsanger.gz |
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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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