Poricoic Acid A attenuated TGF-β1-induced epithelial-mesenchymal transition in renal tubular epithelial cells through SPRY2/ERK signaling pathway. - GreenMedInfo Summary

The progression of renal fibrosis is difficult to reverse, and Poria cocos, one of the main components of Wenyang Zhenshuai Granules, has been shown to be crucial to the development of the epithelial-mesenchymal transition (EMT). This study aimed to examine the molecular mechanism by which Poricoic Acid A (PAA) inhibited the advancement of EMT in renal tubular epithelial (RTE) cells. The protein levels of sprouty RTK signaling antagonist 2 (SPRY2) extracellular regulated protein kinases (ERK), and p-ERK were measured. The EMT progression of RTE cells was evaluated by a series of experiments. The regulatory relationship of PAA to SPRY2 was determined by cycloheximide, molecular docking and drug affinity target stability and immunoprecipitation. The overexpression of SPRY2 or PAA intervention suppressed the HK-2 and NRK-52E cell's viability, proliferation and migration ability of TGF-β1-induced while raising the levels of E-cadherin and decreasing those of collagen I, collagen III, Fibronectin1,α-SMA, Vimentin, ZEB1, Twist, Snail and Slug. PAA was able to be combined with SPRY2 protein. Besides, we found that PAA intervention increased the stability of SPRY2 through the ubiquitin-proteasome pathway, did not affect ERK levels, and reduced the levels of p-ERK. Finally, we found that inhibiting SPRY2 negated the beneficial effect of PAA on TGF-β1-stimulated RTE cells. PAA alleviated the EMT of RTE cells by modulating the SPRY2/ERK pathway.