Upregulation of Cannabinoid Receptor-1 and Fibrotic Activation of Mouse Hepatic Stellate Cells during Schistosoma J. Infection: Role of NADPH Oxidase.

Upregulation of Cannabinoid Receptor-1 and Fibrotic Activation of Mouse Hepatic Stellate Cells during Schistosoma J. Infection: Role of NADPH Oxidase.
Free Radic Biol Med. 2014 Mar 18;
Authors: Wang M, Abais JM, Meng N, Zhang Y, Ritter JK, Li PL, Tang WX
Abstract
The endocannabinoid system (CS) has been implicated in the development of hepatic fibrosis such as schistosomiasis-associated liver fibrosis (SSLF). However, the mechanisms mediating the action of the CS in hepatic fibrosis is unclear. The present study hypothesized that Schistosoma J. infection upregulates cannabinoid receptor 1 (CB1) due to activation of NADPH oxidase leading to a fibrotic phenotype in hepatic stellate cells (HSCs). The SSLF model was developed by infecting mice with Schistosoma J. cercariae in the skin, and HSCs from control and infected mice were then isolated, cultured and confirmed by analysis of HSC markers α-SMA and desmin. CB1 significantly increased in HSCs isolated from mice with SSLF, which was accompanied by a greater expression of fibrotic markers α-SMA, collagen I, and TIMP-1. CB1 upregulation and enhanced fibrotic changes were also observed in normal HSCs treated with soluble egg antigen (SEA) from Schistosoma J.. Electron spin resonance (ESR) analysis further demonstrated that superoxide (O2(-)) production was increased in infected HSCs or normal HSCs stimulated with SEA. Both Nox4 and Nox1 siRNA prevented SEA-induced upregulation of CB1, α-SMA,col...

Source: Free Radical Biology and Medicine - March 18, 2014 Category: Biology Authors: Wang M, Abais JM, Meng N, Zhang Y, Ritter JK, Li PL, Tang WX Tags: Free Radic Biol Med Source Type: research