title: Molecular Survey of Cell Source Usage during Subtotal Hepatectomy-Induced Liver Regeneration in Rats.
abstract: Proliferation of hepatocytes is known to be the main process in the hepatectomy-induced liver regrowth; however, in cases of extensive loss it may be insufficient for complete recovery unless supported by some additional sources e.g. mobilization of undifferentiated progenitors. The study was conducted on rat model of 80% subtotal hepatectomy; the objective was to evaluate contributions of hepatocytes and resident progenitor cells to the hepatic tissue recovery via monitoring specific mRNA and/or protein expression levels for a panel of genes implicated in growth, cell differentiation, angiogenesis, and inflammation. Some of the genes showed distinctive temporal expression patterns, which were loosely associated with two waves of hepatocyte proliferation observed at 2 and 7 days after the surgery. Focusing on genes implicated in regulation of the progenitor cell activity, we came across slight increases in expression levels for Sox9 and two genes encoding tumor necrosis factor-like cytokine TWEAK (Tnfsf12) and its receptor Fn14 (Tnfrsf12a). At the same time, no increase in numbers of cytokeratin 19-positive (CK19+) cells was observed in periportal areas, and no CK19+ cells were found in hepatic plates. Since CK19 is thought to be a specific marker of both cholangiocytes and the hepatic progenitor cells, the data indicate a lack of activation of the resident progenitor cells during recovery of hepatic tissue after 80% subtotal hepatectomy. Thus, proliferation of hepatocytes invariably makes the major contribution to the hepatic tissue recovery, although in the cases of subtotal loss this contribution is distinctively modulated. In particular, induction of Sox9 and TWEAK/Fn14 regulatory pathways, conventionally attributed to progenitor cell activation, may incidentally stimulate mitotic activity of hepatocytes.
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.|Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 1 Ostrovitianov Street, Moscow 117997, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Elchaninov
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.
authors.forename: Timur
authors.initials: T
authors.lastname: Fatkhudinov
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.|Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 1 Ostrovitianov Street, Moscow 117997, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Usman
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.
authors.forename: Evgeniya
authors.initials: E
authors.lastname: Kananykhina
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Arutyunyan
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.|Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.|Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, 1 Ostrovitianov Street, Moscow 117997, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Makarov
authors.affiliation: Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Bolshakova
authors.affiliation: Research Centre of Medical Genetics, 1 Moskvorechie Street, Moscow 115478, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Goldshtein
authors.affiliation: Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of the Russian Federation, 4 Oparina Street, Moscow 117997, Russia.
authors.forename: Gennady
authors.initials: G
authors.lastname: Sukhikh
mesh_terms: D000818:Animals; D015870:Gene Expression; D006498:Hepatectomy / Q000379:methods*; D008115:Liver Regeneration; D051381:Rats