MTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Hauke Busch 

PROVIDER: E-GEOD-54417 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress