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Abnormal Gene Expression Patterns In Regenerating liver of Rats Treated With c‐Met Silencing Constructs
Author(s) -
Paranjpe Shirish,
Bowen William C,
Luo Jianhua,
NejakBowen Kari,
Michalopoulos George K
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a188
Subject(s) - downregulation and upregulation , liver regeneration , biology , cyclin e1 , gene silencing , cell cycle , cdc25a , rna interference , gene expression , gene , cell growth , microbiology and biotechnology , cancer research , cyclin d1 , cell cycle checkpoint , rna , regeneration (biology) , genetics
Liver regeneration after PHx is an extremely complex process requiring interaction and cooperation of many growth factors and cytokines and crosstalk between multiple pathways. HGF/c‐met pathway is among the earliest signaling pathways activated after PHx We utilized RNA interference to silence c‐met in vivo in normal rats, and examined the impact of their elimination on liver regeneration of the liver in a setting not complicated by pathologic alterations of the liver. Analysis of global gene expression in rats treated with ShMet at day one post PHx by microarray indicated dysregulation of many genes involved in cell cycle, stress response, growth regulation. Pro‐apoptotic genes like Caspase 3, Apaf 1, Galectin 1, 2 and 9, Fas, were significantly, upregulated while prosurvival genes like Bcl‐xl, SOD 2, were down regulated. Some of the genes involved in cell cycle that were upregulated were p21, p53 and C/EBP‐alpha while CE/BP‐beta was down regulated. The decrease in the ratio of C/EBP‐alpha to C/EBP‐beta known to occur after PHx was offset in the animals treated with ShMet RNA. Given the dramatic suppression of the BrdU incorporation and absence of mitoses at 24 hours after PHx in the ShMet treated animals, it is significant that there was suppression of expression of cyclin E1 (associated with progression from G1 to S phase).