Inherent control of hepatocyte proliferation after subtotal liver resection

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. © 2019 International Federation for Cell Biology

Elchaninov A. 1, 2 , Fatkhudinov T. 1, 2 , Makarov A. 1, 3 , Vorobieva I.1 , Lokhonina A. 1 , Usman N.1 , Kananykhina E.4 , Vishnyakova P.1 , Nikitina M. 4 , Goldshtein D.5 , Bolshakova G.4 , Glinkina V.3 , Sukhikh G.1
Wiley-Blackwell Publishing Ltd
Number of issue
  • 1 National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of Ministry of Healthcare of Russian Federation, 4 Oparina Street, Moscow, 117997, Russian Federation
  • 2 Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
  • 3 Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 1 Ostrovitianov Street, Moscow, 117997, Russian Federation
  • 4 Research Institute of Human Morphology, 3 Tsurupa Street, Moscow, 117418, Russian Federation
  • 5 Research Center of Medical Genetics, 1 Moscvorechie, Moscow, 115478, Russian Federation
cyclins; cytokines; hepatocytes; liver; proliferation; subtotal resection
Date of creation
Date of change
Short link

Other records