Pentoxifylline Inhibits Liver Fibrosis via Hedgehog Signaling Pathway

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 36; no. 3; pp. 372 - 376
• Main Author: 李慧 华娟 郭春霞 王伟仙 王宝菊 杨东亮 魏屏 卢银平
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.06.2016; Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
• Subjects: Animals; Antigens, Helminth - isolation & purification; Antigens, Helminth - pharmacology; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Line; Culture Media, Conditioned - chemistry; Culture Media, Conditioned - pharmacology; Gene Expression Regulation; Hedgehog; Hedgehog Proteins - agonists; Hedgehog Proteins - antagonists & inhibitors; Hedgehog Proteins - genetics; Hedgehog Proteins - immunology; Hepatic Stellate Cells - cytology; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Humans; Liver Cirrhosis - metabolism; Liver Cirrhosis - parasitology; Liver Cirrhosis - prevention & control; Macrophage Activation - drug effects; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Medicine; Medicine & Public Health; Models, Biological; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Pentoxifylline - pharmacology; Phosphodiesterase Inhibitors - pharmacology; RNA, Messenger - genetics; RNA, Messenger - immunology; Schistosoma japonicum; Schistosoma japonicum - chemistry; Signal Transduction; Tetradecanoylphorbol Acetate - pharmacology; Zinc Finger Protein GLI1 - genetics; Zinc Finger Protein GLI1 - immunology; Zygote - chemistry; 信号通路; 巨噬细胞; 己酮可可碱; 活化过程; 细胞培养; 肝纤维化; 转化生长因子-β; schistosomiasis japonica; pentoxifylline; macrophages; hepatic stellate cells; hedgehog signaling pathway
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-016-1594-7

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog（HH） signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline（PTX） on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate（PMA） was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen（SEA）, and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8（CCK-8） was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and（or） PTX to detect the transforming growth factor-β gene expression. The m RNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The m RNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells（HSCs）. The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.