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Updated: Jul 21, 2026
08:21
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Tumor necrosis factor-alpha inhibits renin gene expression
Vladimir Todorov1, Markus Müller, Frank Schweda
1Institut für Physiologie I, Universität Regensburg, D-93040 Regensburg, Germany. vladimir.todorov@vkl.uni-regensburg.de
Summary
Tumor necrosis factor-alpha (TNF-alpha) inhibits renin gene transcription in kidney cells, potentially impacting blood pressure regulation. Mice lacking TNF-alpha show increased renin levels, suggesting its role in controlling renin synthesis.
Area of Science:
- Nephrology
- Immunology
- Cardiovascular Biology
Background:
- Renin, produced by juxtaglomerular (JG) cells, is crucial for blood pressure regulation.
- Cytokines, like tumor necrosis factor-alpha (TNF-alpha), a key inflammatory mediator, may influence renin production.
- TNF-alpha's role in cardiovascular pathogenesis suggests a potential link to renal renin synthesis.
Purpose of the Study:
- To investigate the effect of TNF-alpha on renin gene transcription in JG cells.
- To determine if TNF-alpha modulates renin synthesis in vivo using TNF-alpha knockout mice.
Main Methods:
- Assessed renin gene expression in As4.1 cells (transformed mouse JG cells) and primary mouse JG cells.
- Utilized TNF-alpha knockout mice and control strains for in vivo analysis.
- Examined renin promoter activity and response to forskolin stimulation.
Main Results:
- TNF-alpha inhibited renin gene expression and transcriptional activity in As4.1 cells.
- TNF-alpha attenuated forskolin-stimulated renin expression in primary JG cells.
- TNF-alpha knockout mice exhibited significantly higher basal renal renin mRNA levels compared to controls.
Conclusions:
- TNF-alpha directly inhibits renin gene transcription at the cellular level.
- TNF-alpha acts as a modulator of renin synthesis in physiological and pathological conditions.
- The study identifies TNF-alpha as a novel regulator of the renin-angiotensin system.
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