Urolithin A attenuates renal fibrosis by inhibiting TGF-β1/Smad and MAPK signaling pathways

Urolithin A (UA) is a bioavailable product of the metabolism of ellagitannins by the gut microbiota, and UA has anti-inflammatory and antioxidant activities. In this study, we investigated whether UA exerted an anti-renal fibrosis effect in a rat model of unilateral ureteral obstruction (UUO) and HK-2 cells treated with TGF-beta 1. In vivo, UA treatment significantly ameliorated UUO-induced renal tissue impairment and decreased macrophage infiltration and proinflammatory cytokine expression. UA attenuated epithelial-mesenchymal transition (EMT) progression by regulating the expression of E-cadherin and alpha-SMA. Moreover, UA treatment significantly decreased the levels of TGF-beta 1, p-Smad2/3, and p-P38/JNK/ERK but increased the level of Smad7. In vitro, UA treatment inhibited TGF-beta 1-induced HK-2 cell fibrosis and proliferation. Furthermore, UA treatment also led to a reduction in the expression of TGF-beta 1, p-Smad3, and p-P38/JNK/ERK, which was accompanied by an increase in the expression of Smad7. These results demonstrate that UA exerts protective effects on renal fibrosis by inhibiting the TGF-beta 1/Smad and MAPK signaling pathways.

Automated summary

UA treatment significantly alleviates renal tissue damage induced by UUO, reducing macrophage infiltration and proinflammatory cytokine expression, inhibiting EMT progression, and regulating the TGF-beta 1/Smad and MAPK signaling pathways to suppress fibrosis.