BACKGROUND

Diabetic kidney disease (DKD) stands as a prominent complication of diabetes, with renal tubulointerstitial fibrosis playing a crucial role in its progression towards end-stage renal disease. Piezo1, a mechanosensitive, non-selective Ca channel, has been definitively linked to the progression of kidney fibrosis.

PURPOSE

The objective of this research is to investigate the pharmacological effects and the underlying mechanisms of lithospermic acid (LA), a polycyclic phenolic carboxylic acid derived from Salvia miltiorrhiza, on DKD-related fibrosis.

METHODS AND RESULTS

To evaluate the protective effect of LA on DKD against renal fibrosis, mice were treated with streptozotocin (STZ) for 7 consecutive days to establish a type 1 diabetes mellitus (T1DM) model. Following the successful establishment of the T1DM model, LA was intraperitoneally administered for an additional 8 weeks. LA significantly attenuated fibrosis formation, inhibited epithelial-mesenchymal transition (EMT) and suppressed the expression of Piezo1 in DKD. In addition, LA decreased activation and expression of Piezo1 in human kidney-2 (HK-2) cells treated with high glucose conditions or Yoda1. Mechanistically, transforming growth factor-β1 (TGF-β1) signaling pathway regulated by Piezo1/Ca axis was attenuated following LA treatment.

CONCLUSION

In summary, our research uncovered the promising potential of LA in mitigating kidney fibrosis, a complication arising from diabetes, through the inhibition of Piezo1. Furthermore, it underscored the pivotal role that Piezo1 plays in the underlying mechanisms leading to renal fibrosis in DKD.