title: Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway.
abstract: 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 mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA 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.
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hua
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Guo
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wei-Xian
authors.initials: WX
authors.lastname: Wang
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Bao-Ju
authors.initials: BJ
authors.lastname: Wang
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Yang
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. pingw_2013@sina.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yinpinglu@163.com.
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Lu
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000302:isolation & purification / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000469:parasitology / Q000517:prevention & control; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012549:Schistosoma japonicum / Q000737:chemistry*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000276:immunology; D015053:Zygote / Q000737:chemistry
chemical_list: D000947:Antigens, Helminth; D017077:Culture Media, Conditioned; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; C509239:SHH protein, human; D000071676:Zinc Finger Protein GLI1; D013755:Tetradecanoylphorbol Acetate; D010431:Pentoxifylline
keywords: hedgehog signaling pathway; hepatic stellate cells; macrophages; pentoxifylline; schistosomiasis japonica