ArticleAmerican journal of physiology. Renal physiology2013
NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Tumor necrosis factor-α in the mediation of acute salt loading induced natriuresis in mice; evidence for its physiological role in regulating kidney function.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- TNF inhibits AQP2 expression via a miR137-dependent pathway.American journal of physiology. Renal physiology · 2024Article
- MicroRNA-195a-5p Regulates Blood Pressure by Inhibiting NKCC2A.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Responses to Ang II (Angiotensin II), Salt Intake, and Lipopolysaccharide Reveal the Diverse Actions of TNF-α (Tumor Necrosis Factor-α) on Blood Pressure and Renal Function.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Induction of renal tumor necrosis factor-α and other autacoids and the beneficial effects of hypertonic saline in acute decompensated heart failure.American journal of physiology. Renal physiology · 2021Article
- MicroRNA-133a-Dependent Inhibition of Proximal Tubule Angiotensinogen by Renal TNF (Tumor Necrosis Factor).Hypertension (Dallas, Tex. : 1979) · 2020Article
- Identification of endogenous 1-aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation.British journal of pharmacology · 2020Article
- Regulation of NKCC2B by TNF-α in response to salt restriction.American journal of physiology. Renal physiology · 2020Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.Physiological genomics · 2018Article
- Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (NaHypertension (Dallas, Tex. : 1979) · 2018Article
- MAD2B promotes tubular epithelial-to-mesenchymal transition and renal tubulointerstitial fibrosis via Skp2.Journal of molecular medicine (Berlin, Germany) · 2016Article
- NFAT5 is protective against ischemic acute kidney injury.Hypertension (Dallas, Tex. : 1979) · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pathways that contribute to TNF production by the kidney are not well defined. Mice given 1% NaCl in the drinking water for 3 days exhibited a 2.5-fold increase in urinary, but not plasma, TNF levels compared with mice given tap water. Since furosemide attenuated the increase in TNF levels, we hypothesized that hypertonic NaCl intake increases renal TNF production by a pathway involving the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). A 2.5-fold increase in NKCC2A mRNA accumulation was observed in medullary thick ascending limb (mTAL) tubules from mice given 1% NaCl; a concomitant 2-fold increase in nuclear factor of activated T cells 5 (NFAT5) mRNA and protein expression was observed in the outer medulla. Urinary TNF levels were reduced in mice given 1% NaCl after an intrarenal injection of a lentivirus construct designed to specifically knockdown NKCC2A (EGFP-N2A-ex4); plasma levels of TNF did not change after injection of EGFP-N2A-ex4. Intrarenal injection of EGFP-N2A-ex4 also inhibited the increase of NFAT5 mRNA abundance in the outer medulla of mice given 1% NaCl. TNF production by primary cultures of mTAL cells increased approximately sixfold in response to an increase in osmolality to 400 mosmol/kgH2O produced with NaCl and was inhibited in cells transiently transfected with a dnNFAT5 construct. Transduction of cells with EGFP-N2A-ex4 also prevented increases in TNF mRNA and protein production in response to high NaCl concentration and reduced transcriptional activity of a NFAT5 promoter construct. Since NKCC2A expression is restricted to the TAL, NKCC2A-dependent activation of NFAT5 is part of a pathway by which the TAL produces TNF in response to hypertonic NaCl intake.
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