Basic—Liver, Pancreas, and Biliary Tractc-Met Confers Protection Against Chronic Liver Tissue Damage and Fibrosis Progression After Bile Duct Ligation in Mice
Section snippets
Generation of Hepatocyte-Specific c-Met Knockout Mice
c-MetloxP/loxP animals11 were first crossed with albumin/α-fetoprotein (AFP) promoter/enhancer12 (Alfp-Cre) or albumin promoter–Cre transgenic animals13 (Alb-Cre). The Alfp-Cre animals express Cre-recombinase during embryonal development, whereas Alb-Cre mice start to express Cre 2 weeks after birth.
BDL
Eight- to 10-week-old mice were subjected to BDL as indicated. BDL was performed by tying the common bile duct using a nonabsorbable filament (Ethicon, Boston, MA). For each of the following
Embryonal Hepatocyte-Specific c-Met Deletion Is Lethal
We first aimed to generate hepatocyte-specific c-Met conditional knockout animals. c-MetloxP/loxP animals were crossed with transgenic animals expressing the Cre-recombinase under the control of an Alfp-Cre construct. Our earlier results showed that this construct results in efficient target gene deletion in hepatocytes at day 12 during embryonic development.14 Interestingly, cross-breeding of c-MetloxP/loxP animals with Alfp-Cre(+/−)/c-MetloxP/wt mice did not result in hepatocyte-specific
Discussion
HGF has been cloned because of its essential role during liver regeneration and has been known for a long time to be strongly involved in liver remodeling and regeneration after hepatic injury. In earlier studies the role of HGF has been investigated by either overexpressing HGF or by deleting its receptor c-Met in whole liver.10, 11, 19 However, only few studies have addressed the role of HGF or c-Met in a specific target cell of the liver (eg, hepatocytes).
HGF and its receptor c-Met have been
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2020, GastroenterologyCitation Excerpt :As such, HSCs are a main source of HGF. Although the role of HSC-derived HGF has not yet been studied, its receptor Met exerts an essential role in hepatocyte regeneration and survival in NASH and other diseases.160–162 HSC-derived collagen promotes hepatocyte survival via Erk163 and possibly via integrin- and mechanosensitive signaling pathways.
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Conflict of interest The authors disclose no conflicts.
Funding This work was supported by the following grants: DFG STR 661/4-1, START 128/06 (to K.S.); SFB 542, C14, SFB/TRR 57, P04 (to C.T.); and the Netherlands Nutrigenomics Consortium (TI Food & Nutrition) (to M.M.). Microarray data: GEO series accession number: GSE13992.