ABSTRACT
Reduced nicotinamide adenine dinucleotide phosphate oxidase (NDAPH oxidase, NOX) is a complex composed of multiple protein subunits and the main enzyme produced by reactive oxygen species (ROS). It has been confirmed that NOXs-mediated oxidative stress is closely related to the occurrence and development of liver fibrosis, and its subunit NOX4 plays a key role. Nox4-derived ROS can not only directly affect the main cell of liver fibrosis ells (HSCs) with significant activation effects but also participate in the continuous activation of HSCs, abnormal proliferation of extracellular matrices(ECMs), apoptosis of hepatocytes, and migration of myofibroblasts(MFBs) by mediating a variety of intracellular signaling pathways including HSCs, which ultimately lead to the occurrence and development of liver fibrosis. This article reviews the role of NOX4-related signaling pathways in the pathogenesis of hepatic fibrosis.
ABSTRACT
Objective To investigate the effect of ursolic acid(UA) on NOX2/ROS/NLRP3 inflammasome activation in carbon tetrachloride(CCl4)-induced liver fibrosis SD rat,and to observe the improvement of collagen deposition in liver tissues. Methods All rats were randomly divided into 3 group:control group,CCl4model group,UA treatment group. Liver fibrosis model SD rats was established by the CCl4-induced method and half of them was used as UA treatment group. Serum ALT was detected by ALT detection kit.The liver pathology and collagen deposition were ob-served by HE and Sirius-red staining. The mRNA expression of Nox2,Nlrp3,Caspase1,IL-1β in liver tissues was detected by RT-qPCR. The protein expression of NOX2,NLRP3,caspase-1 and IL-1β in liver tissues was detected by Western blot and immunohistochemistry and the ROS generation in liver tissues was detected by DCFH-DA fluores-cence probe. Results Compared with control group,in the CCl4model group,the serum ALT was much higher (P<0.05);the Ishak's fibrosis score and collagen deposition was significantly increased(P<0.05) and mRNA of Nox2, Nlrp3,Caspase1,IL-1β was increased.In addition,both the NOX2,NLRP3,caspase-1 p10 and IL-1β protein expres-sion and ROS level (P<0.05) of CCl4model group were significant increased.Compared with CCl4model group,in the UA treatment group Ishak's fibrosis score,collagen deposition and ALT decreased.Both mRNA expression of the Nox2, Nlrp3,Caspase1,IL-1β and protein expression of NOX2,NLRP3,caspase-1 p10 and IL-1β as well as ROS were signif-icant decreased,but the caspase-1 p45 protein level has no difference among all these groups (P>0.05). Conclusions Ursolic acid attenuates the liver injury and reduces the collagen deposition,which may relate to its inhibitory effects on NOX2/ROS/NLRP3 inflammasome activation to reduce IL-1β releasing.