1. RG108 attenuates acute kidney injury by inhibiting P38 MAPK/FOS and JNK/JUN pathways.
- Author
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Kong FX, Liu H, Xu T, Li SJ, Li W, Lu H, Ma NN, Wang YL, Shi JH, Yang YR, and Wang FL
- Subjects
- Animals, Humans, Male, Mice, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, JNK Mitogen-Activated Protein Kinases metabolism, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Kidney pathology, Kidney drug effects, Kidney metabolism, MAP Kinase Signaling System drug effects, Mice, Inbred C57BL, Proto-Oncogene Proteins c-fos metabolism, Proto-Oncogene Proteins c-fos genetics, Phthalimides, Tryptophan analogs & derivatives, Acute Kidney Injury drug therapy, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Cisplatin, p38 Mitogen-Activated Protein Kinases metabolism
- Abstract
Acute kidney injury (AKI) is an important clinical syndrome characterised by a sudden decline in renal function, often accompanied by renal inflammation and tubular epithelial cell damage. It has been reported that inhibiting DNA methylation significantly suppress the progression of AKI. In the current study, we investigate the effect of the DNA methyltransferase (DNMT) inhibitor RG108 in cisplatin- and hypoxia-reoxygenation-induced AKI. The expression of kidney injury molecules and inflammatory factors was examined by immunofluorescence, Western blotting and Real-time PCR. The results demonstrated that RG108 treatment significantly reduced kidney inflammation and injury. Furthermore, RNA-seq analysis was performed to reveal the regulatory mechanism of RG108 in AKI. The expression of the FOS and JUN genes, which are downstream of the MAPK pathway, were significant increased in AKI. Meanwhile, the expression of FOS and JUN were both inhibited by RG108, which is similar to what we found treatment with a specific JNK inhibitor and a specific p38 MAPK inhibitor, and thus attenuated renal inflammation and injury. In conclusion, we suggest that RG108 inhibits P38 MAPK/FOS and JNK/JUN pathways and attenuates renal injury and inflammatory responses. In these results, RG108 may become a novel MAPK pathway inhibitor and a clinical candidate for the treatment of AKI., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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