Conclusion
Our findings provide direct evidence that FGFR1 mediates LPS-induced inflammation leading to renal dysfunction. We also show that AZD4547 is a potential therapeutic agent to reduce inflammatory responses in AKI. Both FGFR1 and AZD4547 may interesting therapeutic options to combat AKI.
Methods
Here, we investigated whether AZD4547 could mitigate inflammatory responses in AKI. C57BL/6 mice were injected with lipopolysaccharide (LPS) to induce AKI. FGFR1 was blocked using AZD4547 or CRISPR/Cas9 genome editing. After immunofluorescent double-staining of kidney tissues showing that P-FGFR1 was localized to renal tubular epithelial cells, a tubular epithelial cell line (NRK-52E) was used for in vitro analysis.
Results
AZD4547 significantly reduced renal inflammation, cell apoptosis, and kidney dysfunction in AKI mice. In vitro, treatment of NRK-52E cells with AZD4547 attenuated LPS-induced inflammatory responses and was associated with downregulated P-FGFR1 levels. These findings were further confirmed in NRK-52E cells by knocking down the expression of FGFR1.