Paeoniflorin inhibits renal fibrosis in MRL/lpr mice via suppression of TGF-β1/Smad2/3 signaling

Lupus nephritis (LN) is a common kidney injury associated with systemic lupus erythematosus (SLE) and represents the most significant cause of disability and mortality in SLE patients. Renal interstitial fibrosis is a common pathological process leading to end-stage renal failure in various chronic kidney diseases. Paeoniflorin (PF) is a water-soluble monoterpenoid glycoside extracted from Paeonia lactiflora . Although there is evidence that PF protects against LN, its underlying mechanisms remain unclear. This study found a significant relationship between TGF-β1 and LN and a good binding activity between PF and the core target proteins of epithelial-mesenchymal transition (EMT) by LncRNA sequencing and molecular docking. After 9 weeks of PF treatment, renal function and structure were significantly improved in MRL/lpr mice, with increased expression of E-cadherin and decreased expression of vimentin and α-SMA. Furthermore, PF further inhibited EMT by increasing E-cadherin expression and reducing the expression of vimentin and α-SMA in TGF-β1-treated HK-2 cells and co-culture of M2c and HK-2 cells. Additionally, PF inhibited the expression of the TGF-β1/Smad2/3 pathway both in vivo and in vitro . Thus, PF may improve renal fibrosis and EMT by inhibiting the TGF-β1/Smad2/3 signaling pathway, thereby to slow down the pathological process of LN fibrosis.