data). Based on these findings, sorafenib can be considered to be more than just an anticancer drug. According to our current understanding, a variety of cytokines are involved in the pathological process of liver diseases, of which TGF-β is the most important inducer.3 Thus, studying TGF-β-induced EMT and apoptosis
in mouse hepatocytes is very important for the development of new and efficacious therapies for fibrosis, cirrhosis, portal hypertension, and other liver diseases. In the past decade, several antifibrotic strategies have been successfully established based on the blockade or elimination of latent TGF-β signaling at various transduction steps. Several gene therapy approaches using dominant-negative TGF-β receptors and BMP-7 have been developed to prevent fibrosis
in different tissues.22, 23 Similarly, ectopic overexpression of Smad7 in the hepatocytes STA-9090 price of transgenic mice was shown to attenuate TGF-β signaling and thereby improve CCl4-induced liver fibrosis.24 In addition to these protein-based Selleck GSK 3 inhibitor therapies, small molecules and biological agents that act on this signaling cascade have shown strong therapeutic potential in clinical settings. However, efficient and well-tolerated antifibrotic drugs are currently lacking. The present study provides a simple and efficient strategy for high-throughput screening of chemicals that interfere with TGF-β signaling. Aside from sorafenib, we have identified several small compounds that inhibit TGF-β signaling using this unbiased cellular screening model. Based on their down-regulation of TGF-β signaling, beneficial effects of these candidates on organ fibrosis could be expected. This expectation has been partially supported by in vivo animal studies showing medchemexpress antifibrotic effects on
experimental hepatic, renal, and pulmonary fibrosis (unpubl. data). A more detailed set of such investigations are currently being performed. In summary, our data provide in vitro evidence that sorafenib inhibits TGF-β signaling and suppresses TGF-β1-induced EMT and apoptosis in mouse hepatocytes. We thank our colleagues Zheng Li, Jing Xie, Jiang-Sha Zhao, Shu-Yi Ji, and Xiao Hu for helpful discussions and technical assistance. We thank Dr. Ye-Guang Chen (Tsinghua Univ., P.R. China) for kindly providing Smad3 antibody. Additional Supporting Information may be found in the online version of this article. “
“A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC). Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included.