Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Sun, X.
Kaempferol ameliorates calcium oxalate crystal-induced renal injury and crystal deposition by attenuating oxidative stress and inflammation through the downregulation of the AR/NOX2 signaling pathway
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 115
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Hutterer Georg
- Pichler Martin
- Zigeuner Richard
- Altmetrics:
- Abstract:
- Background Oxidative stress (OS) and inflammation are thought to be crucial contributors to the process of forming urolithiasis. Methods We used mice models and human kidney-2 (HK-2) cells to explore the role and mechanism of kaempferol in CaOx crystal-induced renal crystal deposition and injury. The crystal deposition in kidney was evaluated by pathologic examination, and renal injury was detected by histological staining and serum neutrophil gelatinase-associated lipocalin, urea nitrogen and creatinine. Crystal adhesion to HK-2 cells was observed by microscopy, and cell injury was detected by flow cytometry. Oxidative stress was measured by flow cytometry, fluorescence imaging and microplate. Immunohistochemistry staining, fluorescence staining, western blot and polymerase chain reaction were used to assess the gene expressions. The mechanism of how androgen receptor (AR) regulates nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) was dissected via chromatin immunoprecipitation and luciferase reporter assay. Results Kaempferol decreased CaOx crystal deposition in mice kidney and crystal adhesion to HK-2 cells. Kaempferol suppressed crystal-induced cell injury, inflammation, and OS in in vivo and in vitro. Moreover, kaempferol inhibited the renal AR expression, and AR could directly bind to the NOX2 promoter to promote NOX2 expression at the transcriptional level. Kaempferol played a key role in inhibiting crystal-induced renal OS and inflammatory injury, and crystal deposition by downregulating the AR/NOX2 signal pathway. Conclusion All in all, this work suggests that kaempferol could inhibit renal crystal-induced injury and crystal deposition by inhibiting OS and inflammation by downregulating the AR/NOX2 signal pathway. Kaempferol may have potential preventive and therapeutic effects for CaOx urolithiasis.