ArticleThe Journal of clinical investigation2000
Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 142 citations in OpenAlex.
- Article
- NSAID-Induced acute kidney injury risk in patients on renin-angiotensin system inhibitors and diuretics: nationwide cohort study.Journal of pharmaceutical health care and sciences · 2025Article
- The Influence of Heat on Pediatric and Perinatal Health: Risks, Evidence, and Future Directions.Journal of clinical medicine · 2025Review
- The NF-κB/FXR/TonEBP pathway protects renal medullary interstitial cells against hypertonic stress.Journal of cellular and molecular medicine · 2024Article
- Role of Changes in State of Bound Water and Tissue Stiffness in Development of Age-Related Diseases.Polymers · 2020Review
- Article
- Differential compensation of two cyclooxygenases in renal homeostasis is independent of prostaglandin-synthetic capacity under basal conditions.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells.The Journal of biological chemistry · 2018Article
- Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Baicalein induces cervical cancer apoptosis through the NF-κB signaling pathway.Molecular medicine reports · 2018Article
- NF-κB-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells.American journal of physiology. Cell physiology · 2017Article
- Article
- Disruption of cyclooxygenase type 2 exacerbates apoptosis and renal damage during obstructive nephropathy.American journal of physiology. Renal physiology · 2015Article
- Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.Pflugers Archiv : European journal of physiology · 2014Article
- mPGES-1-derived PGE2 mediates dehydration natriuresis.American journal of physiology. Renal physiology · 2013Article
- Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.PloS one · 2013Article
- AMPK potentiates hypertonicity-induced apoptosis by suppressing NFκB/COX-2 in medullary interstitial cells.Journal of the American Society of Nephrology : JASN · 2011Article
- Hypotonicity-induced reduction of aquaporin-2 transcription in mpkCCD cells is independent of the tonicity responsive element, vasopressin, and cAMP.The Journal of biological chemistry · 2011Article
- Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB activity.Molecular biology of the cell · 2010Article
- Sirtuins and their relevance to the kidney.Journal of the American Society of Nephrology : JASN · 2010Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2). After dehydration, the maintenance of normal renal function becomes particularly dependent upon PG synthesis. The present studies were designed to examine the potential link between medullary COX1 and COX2 expression in hypertonic stress. In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs). Water deprivation also increases renal NF-kappaB-driven reporter expression in transgenic mice. NF-kappaB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea. RMIC COX2 expression was also induced by driving NF-kappaB activation with a constitutively active IkappaB kinase alpha (IKKalpha). Conversely, introduction of a dominant-negative IkappaB mutant reduced COX2 expression after hypertonicity or IKKalpha induction. RMICs failed to survive hypertonicity when COX2 was downregulated using a COX2-selective antisense or blocked with the selective nonsteroidal anti-inflammatory drug (NSAID) SC58236, reagents that did not affect cell survival in isotonic media. In rabbits treated with SC58236, water deprivation induced apoptosis of medullary interstitial cells in the renal papilla. These results demonstrate that water deprivation and hypertonicity activate NF-kappaB. The consequent increase in COX2 expression favors RMIC survival in hypertonic conditions. Inhibition of RMIC COX2 could contribute to NSAID-induced papillary injury.
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