Title: Clinical and Translational Studies in Fibrosis
Abstract:Background: Inflammatory bowel disease (IBD) is found to be associated with several kinds of liver disease.The purpose of this study is to investigate the role of combination with dextran sodium sulfa...Background: Inflammatory bowel disease (IBD) is found to be associated with several kinds of liver disease.The purpose of this study is to investigate the role of combination with dextran sodium sulfate (DSS) in hepatitis and fibrosis in mice treated by with CCl4.Methods: Male C57BL/6 mice were grouped as follows: Control group (n=10), DSS group (n=10), Olive oil group (n=10), CCl4 group (n=10) and CCl4+DSS group (n=10).Severity of colitis was evaluated by disease activity index (DAI), colon length, colon pathology score, myeloperoxidase (MPO) and histopathology.Haematoxylin and eosin (H&E) staining, Sirius red staining and Masson's trichrome (MT) staining were used to detect liver histopathological changes.Pro-inflammatory cytokines in both colon and liver tissues including TNF-α, IFN-γ and IL-17A were detected by immunohistochemical staining, western blot and real-time Q-PCR, respectively.The protein and mRNA expressions of TGF-β1, α-SMA, collagen I, collagen III, MMP-2 and TIMP-2 in liver tissues were observed by immunohistochemical staining, western blot and real-time Q-PCR, respectively.Results: DSS treatment led to increased BW loss, higher DAI score, shortened colon length, elevated MPO activity, and worsened histologic inflammation in colon.Moreover, TNF-α, IFN-γ and IL-17A expressions in both colon and liver tissues were all enhanced in DSS group.Hepatitis was also found in DSS group as well as CCl4 group and CCl4+DSS group by histological analysis.However, comparing with CCl4 group, hepatitis in CCl4+DSS were more severe, reflected by histology and pro-inflammation cytokines expressions.Increased hepatic fibrosis was observed by Sirius red staining and MT staining, as well as higher levels TGF-β1, α-SMA, collagen I, collagen type III, TIMP-2 and lower level of MMP-2 in liver tissue.Conclusions: The DSS-induced mouse colitis may promote hepatic inflammation and fibrosis in mice treated by CCl4.Read More