ArticleProceedings of the National Academy of Sciences of the United States of America2018
Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Uric acid reduces the expression of aquaporins in renal collecting ducts to increase urine output in hyperuricemia.Frontiers in physiology · 2025Article
- The NF-κB/FXR/TonEBP pathway protects renal medullary interstitial cells against hypertonic stress.Journal of cellular and molecular medicine · 2024Article
- Editorial: Insights in renal and epithelial physiology: 2023.Frontiers in physiology · 2024Article
- The role of the farnesoid X receptor in kidney health and disease: a potential therapeutic target in kidney diseases.Experimental & molecular medicine · 2023Review
- Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis.eLife · 2023Article
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Bile acid receptors and renal regulation of water homeostasis.Frontiers in physiology · 2023Review
- Bile acids and salt-sensitive hypertension: a role of the gut-liver axis.American journal of physiology. Heart and circulatory physiology · 2022Review
- Farnesoid X receptor: a potential therapeutic target in multiple organs.Histology and histopathology · 2020Review
- Activation of farnesoid X receptor (FXR) induces crystallin zeta expression in mouse medullary collecting duct cells.Pflugers Archiv : European journal of physiology · 2020Article
- Update on FXR Biology: Promising Therapeutic Target?International journal of molecular sciences · 2018Review
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.
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