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Journal of Gastroenterology and Digestive Diseases | Volume 3
May 25-26, 2018 | New York, USA
World Liver Conference 2018
Chronic liver injury can lead to inflammation, fibrosis,
cirrhosis, and tumorigenesis. Since TM4SF5, a tetraspan
(in) with four transmembrane domains is shown to be
involved in liver fibrosis, it is reasonable to consider that
TM4SF5 can play roles in important roles development
of liver diseases. In CCl4 -administrated animal livers, the
pattern of TM4SF5 expression along the fibrotic septa was in
parallel to those of TGFβ1, α-SMA, and collagen I deposition.
TM4SF5 is induced by signaling activities of TGFβ1- and
EGFR-mediated signaling pathways. Therefore, in this
current study, we further explored how TM4SF5 is involved
in development of liver fibrosis and HCC, using in vitro cell
and in vivo animal systems in addition to human tissues.
Primary hepatocytes isolated from mice treated with CCl4
for four or 16 weeks, to mimic fibrotic and cirrhotic livers,
respectively, showed enhanced TM4SF5, α-SMA, collagen I,
and laminins expression, in addition to increased c-Src and
STAT3 activities. Suppression or inhibition of TM4SF5, c-Src,
or STAT3 could result in blocking of collagen I and laminin
expression. Furthermore, when CCl4 administration was
performed together with IP or intratumoral treatment of anti-
TM4SF5 antibody, the mice showed reduced development
of CCl4-mediated fibrosis phenotypes in livers and tumor
formation by xenografts, in addition to reduced STAT3
signaling activity and ECM deposition. These observations
suggest that TM4SF5 may be involved in the development
of fibrosis and tumorigenesis, via its roles in ECM induction
through c-Src and STAT signaling pathways.
Speaker Biography
Jung Weon Lee has completed his PhD from University of North Carolina at Chapel Hill,
NC, USA and Post-doctoral studies from MSKCC at NY. These days, his research group
mostly focuses on the roles of a tetraspanin, TM4SF5, in NASH, fibrosis, tumorigenesis
and metastasis, and on the anti-TM4SF5 reagents to block TM4SF5-mediated liver
diseases, in either 2D or extracellular matrix-surrounded 3D culture conditions via
biochemical, cell biological and molecular biological approaches in addition to animal
models, and clinical samples for the fibrotic and tumor models or patients (Lab
homepage: . He has published more than 100 papers
in reputed journals.
e:
TM4SF5 drives aggravation from nonalcoholic fatty to fibrotic and cancerous liver
Jung Weon Lee
Seoul National University, South Korea