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Inherent control of hepatocyte proliferation after subtotal liver resection
Author(s) -
Elchaninov Andrey,
Fatkhudinov Timur,
Makarov Andrey,
Vorobieva Iva,
Lokhonina Anastasia,
Usman Natalia,
Kananykhina Evgeniya,
Vishnyakova Polina,
Nikitina Maria,
Goldshtein Dmitry,
Bolshakova Galina,
Glinkina Valeria,
Sukhikh Gennady
Publication year - 2020
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11203
Subject(s) - hepatocyte , liver regeneration , hepatectomy , cell growth , hepatocyte growth factor , oncogene , biology , cyclin d1 , cell cycle , gene expression , cyclin , growth factor , cancer research , endocrinology , medicine , receptor , microbiology and biotechnology , gene , resection , regeneration (biology) , surgery , genetics , in vitro
At the normal physiological conditions, hepatocytes predominantly reside in G0 phase of cell cycle; they actively proceed to G1 phase upon damage to the organ. As it was shown in experiments with restoration of liver mass in rats after subtotal hepatectomy (resection of 80% of the organ mass may be considered as a model of the ‘small for size’ liver syndrome), the growth inhibition is due to prolonged arrest of hepatocyte proliferation, molecular mechanisms of which remain understudied. In a rat model of liver regeneration after surgical removal of 80% of its mass, we observe a delayed onset of hepatocyte proliferation: Ki67 + hepatocytes begin to appear as late as at 30 h after liver subtotal resection. Their appearance coincides with the beginning of transcription of genes for cyclins A2, B1, D 1 , and E 1 at 24–30 h after surgery. The corresponding increase in concentrations of cyclin D 1 and E proteins is further delayed till 48 h after liver resection. We have also observed a prolonged decrease in the expression of proto‐oncogene c‐met (the hepatocyte growth factor receptor‐encoding gene Met ), an increase in expression of the transforming growth factor β1 (TGFβ 1 ) receptor‐encoding gene Tgfbr2 . At the same time, irreversible block of hepatocyte proliferation is prevented by expression of certain factors, notably of the TWEAK/Fn14 signaling pathway: concentrations of the corresponding proteins in remnant livers have peaked from 24 to 48 h after liver subtotal resection.