- 作者: Satish Kumar Devarapu, Julia Felicitas Grill, Junhui Xie, Marc Weidenbusch, Mohsen Honarpisheh, Volker Vielhauer, Hans-Joachim Anders and Shrikant R. Mulay
- 作者服務機構: 1. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany 2. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3. Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Schillerstr. 42, D-80336 Munich, Germany
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: Crystal nephropathy, Ischemia reperfusion injury, Chronic kidney injury, Anti-GBM, Tumor necrosis factor, Tumor necrosis factor ligands, TNF superfamily