This study investigates the protective effect of indolepropionic acid (IPA) on renal fibrosis caused by unilateral ureteral obstruction (UUO), with a focus on the Nrf2 signaling pathway.
Methods
A UUO model was established in 30 male SD rats (6 weeks old) via unilateral ureteral ligation. Rats were divided into sham, model, L-IPA, M-IPA, and H-IPA groups. Pathological changes and protein expressions in renal tissues were analyzed. In vitro, HK-2 cells were cultured and subjected to hypoxia for 24 h. Cells were divided into control, model, model + IPA, and model + IPA + ML385 (Nrf2 inhibitor) groups. Fibrosis and Nrf2-related protein expressions were assessed.
Results
In vivo, the model group exhibited severe renal damage, accompanied by increased oxidative stress and inflammatory response. The expression of α-SMA, FN, Snail1, Smad3, TGF-β1, Keap1, and HIF-1α was elevated, while Nrf2 and HO-1 levels were decreased, all of which were reversed by IPA treatment. In vitro, IPA reversed the changes in fibrosis-related proteins, while this protective effect was blocked by ML385.
Conclusion
IPA ameliorates renal fibrosis by activating the Nrf2 pathway, offering a potential therapeutic strategy for renal injury.
Graphic summary
Indolepropionic acid activates the Nrf2 signaling pathway, inhibits the expression of renal fibrosis-related proteins, and alleviates renal fibrosis.
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