biostudies-literatureXu SNational Natural Science Foundation of China5600-5605https://www.ebi.ac.uk/biostudies/studies/S-EPMC6003498biostudies-literatureUnknown115(21)Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a maProceedings of the National Academy of Sciences of the United States of AmericaFarnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.PMC600349881570636/81722010/81390351/91639201Wang BWei YGustafsson JAWang NHuang SXing MLi YGuan YDu CZhang XXu SZheng FLuan ZChen TfalseFarnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a ma2018-01-01T00:00:00Z2018 May2025-04-25T19:56:01.582Z2019-03-27T00:08:05ZS-EPMC60034982973988910.1073/pnas.1803945115