Tumor necrosis factor superfamily ligand mRNA expression profiles differ between humans and mice during homeostasis and between various murine kidney injuries
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Updated: Feb 22, 2026
Quantitative Real-Time PCR Evaluation of microRNA Expressions in Mouse Kidney with Unilateral Ureteral Obstruction
Published on: August 27, 2020
Satish Kumar Devarapu1, Julia Felicitas Grill1, Junhui Xie1,2
1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
Background:
Several tumour necrosis factor (TNF) based therapeutics have already been approved for human use and several others are emerging. Therefore, we determined the mRNA expression levels of the TNF superfamily ligands (TNFSF) - e.g. TNF-α, lymphotoxin (LT)-α, LT-β, Fas-L (CD95-L), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related weak inducer of apoptosis (TWEAK), 4-1BBL, OX40-L (CD252) and amyloid precursor protein (APP) in healthy human and mouse solid organs.
Methods:
We used quantitative real time-PCR to analyse mRNA expression levels of TNFSF ligands. Murine models of acute ischemic renal injury, chronic oxalate nephropathy, and immune complex glomerulonephritis were used. Renal injury was assessed by PAS staining, and infiltrating immune cells were analysed by immunohistochemistry. Data was analysed using non-parametric ANOVA (non-parametric; Kruskal-Wallis test).
Results:
We observed significant differences in the mRNA expression levels of TNFSF ligands in human and mouse solid organs. Furthermore, we determined their mRNA expressions during acute and chronic kidney injuries in mice. Our data demonstrate that the mRNA expression levels of TNFSF vary depending on the type of tissue injury - for example, acute ischemic renal injury, chronic crystalline nephropathy, and immune complex glomerulonephritis. In addition, we observed that mRNA expressions of TNFSF ligands are differentially regulated during the course of a transient ischemic renal injury (IRI) and chronic kidney modelling. We observed that TNF-α, LT-β, and 4-1BBL were significantly upregulated during the progression of IRI and crystal-induced chronic kidney disease (CKD), whereas only 4-1BBL and TNF-α were significantly upregulated and LT-β was significantly downregulated during the progression of immune complex glomerulonephritis. The mRNA expression of Fas-L was higher during IRI whereas it decreased in a time dependent manner during the progression of crystal-induced CKD.
Conclusion:
We conclude that the injury- and species-specific differences of TNFSF ligands must be considered in order to avoid the misinterpretation and wrong conclusions during data extrapolation between species.
Insights
Tumor necrosis factor superfamily ligand (TNFSF) mRNA expression differs significantly between human and mouse organs and varies with kidney injury type. These species- and injury-specific differences are crucial for accurate interpretation of therapeutic research.
Area of Science:
- Immunology
- Molecular Biology
- Nephrology
Background:
- Several tumor necrosis factor (TNF)-based therapeutics are approved or emerging for human use.
- Investigating TNF superfamily ligands (TNFSF) mRNA expression in healthy human and mouse solid organs is essential.
- Key TNFSF members include TNF-α, lymphotoxin (LT)-α, LT-β, Fas-L, TNF-related apoptosis-inducing ligand (TRAIL), TWEAK, 4-1BBL, OX40-L, and amyloid precursor protein (APP).
Purpose of the Study:
- To determine and compare mRNA expression levels of TNFSF ligands in healthy human and mouse solid organs.
- To analyze the differential mRNA expression of TNFSF ligands during various kidney injury models in mice.
- To understand the species- and injury-specific regulation of TNFSF ligands in the context of kidney disease.
Main Methods:
- Quantitative real-time PCR was employed to analyze mRNA expression levels of TNFSF ligands.
- Murine models of acute ischemic renal injury, chronic oxalate nephropathy, and immune complex glomerulonephritis were utilized.
- Renal injury and immune cell infiltration were assessed using PAS staining and immunohistochemistry, respectively. Data analysis involved non-parametric ANOVA (Kruskal-Wallis test).
Main Results:
- Significant differences in TNFSF ligand mRNA expression were observed between human and mouse solid organs.
- mRNA expression levels of TNFSF ligands varied distinctly depending on the type of kidney tissue injury.
- Specific TNFSF ligands like TNF-α, LT-β, and 4-1BBL showed differential upregulation or downregulation during acute and chronic kidney injury progression.
Conclusions:
- Injury- and species-specific differences in TNFSF ligand expression are significant.
- These variations must be considered to prevent misinterpretation when extrapolating data between species.
- Understanding these differences is critical for the development and application of TNF-based therapeutics.
