Bridging the Gap between TGF-β/Smad Signalling and Tumorigenesis Arising from Clonorchis sinensis Induced Hepatic Fibrosis

Ika Nurzijah, Dina Ratna Juwita

Abstract


Clonorchiasis is a parasitic infection caused by food borne trematode, Clonorchis sinensis that is mainly prevalent in Asian countries, including South Korea, China, northern Vietnam, Japan, as well as far-eastern Russia, in which over 35 million people are the casualties. Clonorchiasis is characterized by the development of hepatic fibrosis. Upon chronic liver injury following the C. sinensis infection, hepatic fibrosis develops into cholangiocarcinoma with a concomitant genetic and epigenetic mutations. Cholangiocarcinoma represents important clinical manifestation of C. sinensis infection and causes high rate of morbidity. TGF- β/Smad signalling is known to initiate hepatic fibrosis following the hepatic injury. However, little is known about the role of TGF- β/Smad signalling during C. sinensis induced hepatic injury and the underlying contribution of TGF- β/Smad signalling in the development of cholangicarcinoma. The expression dynamic of TGF-β/Smad signalling and their role in the development of hepatic fibrosis in C. sinensis infected BALB/c mice have been investigated. Concomitantly but irrespective to C. sinensis infection, the role of hepatic epithelial TGF-β during hepatic fibrosis and the development of cholangiocarcinoma arising from hepatic epithelial cells have also been dissected. Both findings will be reviewed in this paper. Thereby, the link between TGF-β/Smad signalling, hepatic fibrosis during C sinensis infection, and cholangiocarcinoma could be drawn clearly.

Keywords: Clonorchis sinensis, TGF-β/Smad signalling, Hepatic fibrosis, Cholangiocarcinoma


Full Text:

PDF

References


Barros, A.F., Oliveira, S.A., Carvalho, C.L., Silva, F.L., Souza, V.C.A.D., Silva, A.L.D., et al., 2014, Low Transformation Growth Factor-Β1 Production and Collagen Synthesis Correlate With the Lack of Hepatic Periportal Fibrosis Development in Undernourished Mice Infected with Schistosoma Mansoni, Mem. Inst. Oswaldo Cruz, 109(2), 210-219. Link

Chen, B.L., Peng, J., Li, Q.F., Yang, M., Wang, Y. and Chen, W., 2013, Exogenous Bone Morphogenetic Protein-7 Reduces Hepatic Fibrosis in Schistosoma Japonicum-Infected Mice via Transforming Growth Factor-b/Smad Signalling, World J. Gastroenterol., 19(9), 1405-1415. CrossRef

Hernandez-Gea, V. and Friedman, S.L., 2011, Pathogenesis of Liver Fibrosis, Annu. Rev. Pathol., 6, 425-456. CrossRef

Hong, S.T. and Fang, Y., 2012, Clonorchis Sinensis and Clonorchiasis, An Update, Parasitol. Int., 61(1), 17-24. CrossRef

Hu, F., Hu, X., Ma, C., Zhao, J., Xu, J. and Yu, X., 2009, Molecular Characterization of A Novel Clonorchis Sinensis Secretory Phospholipase A 2 and Investigation of Its Potential Contribution to Hepatic Fibrosis, Mol. Biochem. Parasitol., 167(2), 127-134. CrossRef

Keiser, J. and Utzinger, J., 2009, Food-borne Trematodiases. Clin. Microbiol. Rev., 22(3), 466-483. CrossRef

Mao, Q., Xie, Z., Wang, X., Chen, W., Ren, M., Shang, M., et al., 2015, Clonorchis Sinensis Ferritin Heavy Chain Triggers Free Radicals and Mediates Inflammation Signaling in Human Hepatic Stellate Cells, Parasitol. Res., 114(2), 659-670. CrossRef

Minoo, P. and Li, C., 2010, Cross-Talk Between Transforming Growth Factor-Β and Wingless/Int Pathways in Lung Development and Disease, Int. J. Biochem. Cell Biol., 42(6), 809-812. CrossRef

Mu, X., Pradere, J.P., Affò, S., Dapito, D.H., Friedman, R., Lefkovitch, J.H., et al., 2016, Epithelial Transforming Growth Factor-Β Signaling does not Contribute to Liver Fibrosis but Protects Mice from Cholangiocarcinoma, Gastroenterology, 150(3), 720-733. CrossRef

Ong, C.K., Subimerb, C., Pairojkul, C., Wongkham, S., Cutcutache, I., Yu, W., et al., 2012, Exome Sequencing of Liver Fluke-associated Cholangiocarcinoma, Nat. Genet., 44(6), 690-693. CrossRef

Padua, D. and Massagué, J., 2009, Roles of TGFβ in Metastasis, Cell Res., 19(1), 89-102. CrossRef

Qian, M. B., 2017, Neglected Tropical Diseases and Global Burden of Disease in China, Infect. Dis. Poverty., 6(1), 25. CrossRef

Wang, J., Zhang, C., Wei, X., Blagosklonov, O., Lv, G., Lu, X., et al., 2013, TGF-β and TGF-β/Smad Signaling in the Interactions between Echinococcus multilocularis and Its Hosts, PLoS One, 8(2), e55379. CrossRef

Warmflash, A., Zhang, Q., Sorre, B., Vonica, A., Siggia, E.D. and Brivanlou, A.H., 2012, Dynamics of TGF-β Signaling Reveal Adaptive and Pulsatile Behaviors Reflected in The Nuclear Localization of Transcription Factor Smad4, Proc. Natl. Acad. Sci. USA., 109(28), E1947-E1956. CrossRef

Wu, W., Qian, X., Huang, Y. and Hong, Q., 2012, A Review of the Control of Clonorchiasis Sinensis and Taenia Solium Taeniasis/Cysticercosis in China, Parasitol. Res., 111(5), 1879-1884. CrossRef

Wynn, T.A. and Ramalingam, T.R., 2012, Mechanisms of Fibrosis: Therapeutic Translation for Fibrotic Disease, Nat. Med., 18(7), 1028-1040. CrossRef

Xu, J., Lamouille, S. and Derynck, R., 2009, TGF-β-Induced Epithelial to Mesenchymal Transition, Cell Res., 19(2), 156-172. CrossRef

Yan, C., Wang, L., Li, B., Zhang, B.B., Zhang, B., Wang, Y.H., et al., 2015, The Expression Dynamics of Transforming Growth Factor-b/Smad Signaling in the Liver Fibrosis Experimentally Caused by Clonorchis Sinensis, Parasit Vectors., 8(1), 70. CrossRef

Yin, Y. and Shen, W.H., 2008, PTEN: A New Guardian of the Genome, Oncogene, 27(41), 5443-5453. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev9iss1pp41-46

Copyright (c) 2018 Ika Nurzijah

Indexed by:

                 

                  

   

 

Indonesian Society for Cancer Chemoprevention