scholarly journals Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

Hepatology ◽  
2007 ◽  
Vol 46 (6) ◽  
pp. 1993-2002 ◽  
Author(s):  
Kwang-Hoon Song ◽  
Ewa Ellis ◽  
Stephen Strom ◽  
John Y.L. Chiang
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Hepatocytes ◽  
Growth Factor Signaling ◽  
Hepatocyte Growth ◽  
Growth Factor Signaling Pathway

Increased Engraftment of Hepatic Progenitors After Activation of the Hepatocyte Growth Factor Signaling Pathway by Protein Transduction

2009 ◽  
Vol 234 (9) ◽  
pp. 1102-1108 ◽  
Author(s):  
Guillaume Kellermann ◽  
Lyes Boudechiche ◽  
Anne Weber ◽  
Michelle Hadchouel
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Cell Types ◽  
Cell Surface Receptor ◽  
Migration And Invasion ◽  
Protein Transduction ◽  
Growth Factor Signaling ◽  
Hepatocyte Growth

Cell transplantation has become a major focus in biomedical research. However, efficient engraftment in solid tissues remains a challenge. Hepatocyte growth factor (HGF) signaling increases survival, proliferation, migration, and invasion of many cell types through Met, its cell surface receptor. Therefore, activation of this signaling pathway may improve the ability of many cells to be transplanted. We constructed a constitutively activated form of Met (Tpr-Met) fused to the protein transduction domain of HIV-TAT to activate the HGF/Met pathway for a few hours following cell injection. Matrix-assisted refolding was used to renature TAT-Tpr-Met protein, which was efficiently delivered into cells and recapitulated several biological functions of Met in vitro. Furthermore, treatment of hepatic progenitors with this molecule for one hour before transplantation significantly improved engraftment efficiency (31% untreated cells, 58% treated cells). These findings suggest that the transient transfer of Tpr-Met may provide a new approach to increase the proportion of successfully engrafted cells.

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