Epithelial-mesenchymal transition (EMT) is correlated with NAPDH oxidase (NOX)-derived
reactive oxygen species (ROS). The ROS-induced NOD-like receptor pyrin domain containing-3
(NLRP3) inflammasome is a novel mechanism of EMT. Angiotensin II (AngII) induces EMT
by regulating intracellular ROS. Nevertheless, it has not been reported whether AngII
could induce hepatocyte EMT. Angiotensin-(1-7) [Ang-(1-7)] can inhibit the effects
of AngII via a counter-regulatory mechanism. However, whether Ang-(1-7) attenuated
the effects of AngII on hepatocyte EMT remains unclear. The aim of this study was
to determine whether Ang-(1-7) attenuated AngII-induced hepatocyte EMT by inhibiting
the NOX-derived ROS-mediated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, two animal
models were established. In the first model, rats were infused AngII. In the second
model, Ang-(1-7) was constantly infused into double bile duct ligated (BDL) rats.
In vitro, hepatocytes were pretreated with antioxidant, NLRP3 siRNA, NOX4 siRNA, or
Ang-(1-7) before exposure to AngII. In vitro, AngII induced hepatocyte EMT, which
was inhibited by N-acetylcysteine (NAC), diphenylene iodonium (DPI), and NOX4 siRNA.
NLRP3 inflammasome, which was activated by hydrogen peroxide (H2O2), mediated AngII-induced
hepatocyte EMT. Ang-(1-7) suppressed AngII-induced EMT by inhibiting the NOX-derived
H2O2-activated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, infusion of AngII induced
activation of H2O2-correlated NLRP3 inflammasome in rat livers and accumulation of
α-collagen I (Col1A1) in hepatocytes. Infusion of Ang-(1-7) alleviated BDL-induced
liver fibrosis and inhibited the expression of Col1A1 and the activation of NLRP3
inflammasome in hepatocytes. Ang-(1-7) attenuated AngII-induced hepatocyte EMT by
inhibiting the NOX-derived H2O2-activated NLRP3 inflammasome/IL-1ß/Smad circuit.