Hepatic microenvironment underlies fibrosis in chronic hepatitis B patients
Qunyan Yao, Yadong Feng, Pei Han, Feng Yang, Guangqi Song
Abstract
BACKGROUND: microenvironment in order to design novel therapeutics and identify molecular biomarkers to stratify patients is urgently required. AIM: To examine a subset of pre-selected microenvironment factors of chronic HBV patients that may underlie fibrosis, with a focus on fibroblast activation. METHODS: study. Using different recombinant cytokines and growth factors or their combination, we studied how these factors interacted with LX-2 cells and pinpointed the cross-talk between the aforementioned factors and screened the most important factors. RESULTS: Of the secreted factors examined, transforming growth factor (TGF)-β1, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were increased in patients with advanced fibrosis. We found that besides TGF-β1, IL-1β can also induce a profibrotic cascade by stimulating the expression of connective tissue growth factor and platelet-derived growth factor (PDGF) in LX-2 cells. Furthermore, the proinflammatory response can be elicited in LX-2 cells following treatment with IL-1β and TNF-α, suggesting that stellate cells can respond to proinflammatory stimuli. By combining IL-1β and TGF-β1, we observed not only fibroblast activation as shown by αlpha-smooth muscle actin and PDGF induction, but also the inflammatory response as shown by increased expression of IL-1β. CONCLUSION: microenvironment for HBV-induced liver fibrosis, not only TGF-β1 but also IL-1β should be considered as a necessary environmental factor.