ArticleAmerican journal of nephrology2014
The role of tumor necrosis factor alpha in regulating the expression of Tamm-Horsfall Protein (uromodulin) in thick ascending limbs during kidney injury.
Article in American journal of nephrology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- The natural immune molecules urinary Tamm-Horsfall protein and pentraxin 3 as predictors for recurrent urinary tract infection severity: a single-center self-control study.Renal failure · 2025Article
- Nephroprotective effects ofAnnals of medicine and surgery (2012) · 2025Article
- Decreased urinary uromodulin is potentially associated with acute kidney injury: a systematic review and meta-analysis.Journal of intensive care · 2021Article
- Bile and urine peptide marker profiles: access keys to molecular pathways and biological processes in cholangiocarcinoma.Journal of biomedical science · 2020Article
- Uromodulin (Tamm-Horsfall protein): guardian of urinary and systemic homeostasis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Review
- Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats.Frontiers in physiology · 2020Article
- Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney.Journal of the American Society of Nephrology : JASN · 2018Article
- Tamm-Horsfall Protein is a Potent Immunomodulatory Molecule and a Disease Biomarker in the Urinary System.Molecules (Basel, Switzerland) · 2018Review
- Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.Molecules (Basel, Switzerland) · 2017Article
- Tubular cross talk in acute kidney injury: a story of sense and sensibility.American journal of physiology. Renal physiology · 2015Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundTamm-Horsfall Protein (THP) is a glycoprotein expressed exclusively by cells of the thick ascending loop (TAL) of Henle. THP has a protective role in acute kidney injury (AKI), and its expression is downregulated in the early stages of injury. Tumor necrosis factor alpha (TNFα) is a cytokine endogenously expressed by the TAL and is also induced by AKI. Therefore, we hypothesized that TNFα is a key regulator of THP expression.
methodsWe used a mouse model of AKI (ischemia-reperfusion injury, IRI) and a cell culture system of a TAL cell line (MKTAL).
resultsWe show that TNFα is upregulated by TAL cells early after AKI in vivo. The expression of THP and its transcription factor Hepatocyte nuclear factor 1β (HNF1β) were concomitantly decreased at the peak of injury. Furthermore, recombinant TNFα inhibits significantly, and in a dose-dependent manner, the expression of THP, but not HNF1β in MKTAL cells. Interestingly, neither TNFα neutralization nor genetic deletion of TNFα increased THP or HNF levels after injury in vivo.
conclusionOur data suggest that TNFα can inhibit the expression of THP in TAL cells via an HNF1β-independent mechanism, but the downregulation of THP expression in the early AKI does not depend on TNFα. We propose that TNFα regulates THP expression in a homeostatic setting, but the impact of TNFα on THP during kidney injury is superseded by other factors that could inhibit HNF1β-mediated expression of THP.
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