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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+Show Affiliations

Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Institute of Infection and Immunology, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27376806

Citation

Li, Hui, et al. "Pentoxifylline Inhibits Liver Fibrosis Via Hedgehog Signaling Pathway." Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban, vol. 36, no. 3, 2016, pp. 372-376.
Li H, Hua J, Guo CX, et al. Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway. J Huazhong Univ Sci Technol Med Sci. 2016;36(3):372-376.
Li, H., Hua, J., Guo, C. X., Wang, W. X., Wang, B. J., Yang, D. L., ... Lu, Y. P. (2016). Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway. Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban, 36(3), pp. 372-376. doi:10.1007/s11596-016-1594-7.
Li H, et al. Pentoxifylline Inhibits Liver Fibrosis Via Hedgehog Signaling Pathway. J Huazhong Univ Sci Technol Med Sci. 2016;36(3):372-376. PubMed PMID: 27376806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pentoxifylline inhibits liver fibrosis via hedgehog signaling pathway. AU - Li,Hui, AU - Hua,Juan, AU - Guo,Chun-Xia, AU - Wang,Wei-Xian, AU - Wang,Bao-Ju, AU - Yang,Dong-Liang, AU - Wei,Ping, AU - Lu,Yin-Ping, Y1 - 2016/07/05/ PY - 2015/04/24/received PY - 2016/04/22/revised PY - 2016/7/5/entrez PY - 2016/7/5/pubmed PY - 2017/4/4/medline KW - hedgehog signaling pathway KW - hepatic stellate cells KW - macrophages KW - pentoxifylline KW - schistosomiasis japonica SP - 372 EP - 376 JF - Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban JO - J. Huazhong Univ. Sci. Technol. Med. Sci. VL - 36 IS - 3 N2 - 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. SN - 1993-1352 UR - https://www.unboundmedicine.com/medline/citation/27376806/Pentoxifylline_inhibits_liver_fibrosis_via_hedgehog_signaling_pathway_ L2 - https://doi.org/10.1007/s11596-016-1594-7 DB - PRIME DP - Unbound Medicine ER -