Alantolactone alleviates epithelial-mesenchymal transition by regulating the TGF-(3/STAT3 signaling pathway in renal fibrosis

Objective: The epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) plays a crucial role in renal interstitial fibrosis and inflammation, which are key components of chronic kidney disease (CKD). Alantolactone, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), is used in Chinese herbal medicine. Despite its use, the effects of alnatolactone on EMT of RTECs has not been fully elucidated. Methods: In this study, we investigated the potential of alantolactone to EMT in vivo and in vitro. Our experiments were performed using a unilateral ureteral obstruction (UUO) models and HK-2 cells, RTECs, treated with transforming growth factor (TGF-(3). Results: Alantolactone decreased tubular injury and reduced the expression of vimentin, a key EMT marker, while increasing E-cadherin expression in UUO kidneys. Similarly, in RTECs, alantolactone inhibited TGF-(3-induced EMT and its markers. Furthermore, alantolactone attenuated UUO- and TGF-(3-induced STAT3 phosphorylation both in vivo and in vitro, and inhibited the expression of TWIST, an EMT transcription factor, in both models. Conclusion: Alantolactone improves EMT in RTECs by inhibiting STAT3 phosphorylation and Twist expression, suggesting its potential as a therapeutic agent for kidney fibrosis.