Fig 10. Piceatannol suppresses renal fibrosis by downregulation of the p38-MAPK/HDAC4/5 pathway.
Fibrotic stress such as UUO can induce TGF-β1 expression, which causes phosphorylation and upregulation of Smad2/3 or MAPK (JNK2, ERK1/2, or p38) protein expression. It also increases the expression of class II HDACs (HDAC4/5). Piceatannol attenuates the activation of p38-MAPK signaling and the increased HDAC4/5 expression, but not the activation of the TGF-β1/Smad3 signaling pathway. However, whether a direct association between HDAC4/5 and MAPK signaling or between HDAC4/5 and renal fibrosis exists remains unknown. TβRII and TβRI indicate TGFβ receptor II and TGFβ receptor I, respectively.