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

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

lncRNA NEAT1/miR‐495‐3p regulates angiogenesis in burn sepsis through the TGF‐β1 and SMAD signaling pathways

“…TGF‐β can simultaneously promote angiogenesis and antiangiogenesis, and these opposing effects depend on different TGF‐β receptors and the phosphorylation of different downstream SMADs 34 . SMAD1/5/8 phosphorylation via TGF‐β/ALK1 contributes to angiogenesis, whereas SMAD2/3 phosphorylation via TGF‐β/ALK5 inhibits angiogenesis and leads to blood vessel maturation 35 . In this study, we found that downregulation of NEAT1 could substantially inhibit the TGF‐β1 signaling pathway activation, with phosphorylation of SMAD1 and SMAD5 in HUVECs, which could serve as a potential method to promote angiogenesis in BS.…”