Alantolactone alleviates epithelial-mesenchymal transition by regulating the TGF-β/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 and . Our experiments were performed using a unilateral ureteral obstruction (UUO) models and HK-2 cells, RTECs, treated with transforming growth factor (TGF-β).

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-β-induced EMT and its markers. Furthermore, alantolactone attenuated UUO- and TGF-β-induced STAT3 phosphorylation both and , 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.