Amnion ; metabolism ; physiology ; Female ; Hepatectomy ; Humans ; Liver Regeneration ; physiology ; Pregnancy ; Wound Healing ; physiology

Mesothelial cells (MCs) cover the surface of visceral organs and the parietal walls of cavities, and they synthesize lubricating fluids to create a slippery surface that facilitates movement between organs without friction. Recent studies have indicated that MCs play active roles in liver development, fibrosis, and regeneration. During liver development, the mesoderm produces MCs that form a single epithelial layer of the mesothelium. MCs exhibit an intermediate phenotype between epithelial cells and mesenchymal cells. Lineage tracing studies have indicated that during liver development, MCs act as mesenchymal progenitor cells that produce hepatic stellate cells, fibroblasts around blood vessels, and smooth muscle cells. Upon liver injury, MCs migrate inward from the liver surface and produce hepatic stellate cells or myofibroblast depending on the etiology, suggesting that MCs are the source of myofibroblasts in capsular fibrosis. Similar to the activation of hepatic stellate cells, transforming growth factor β induces the conversion of MCs into myofibroblasts. Further elucidation of the biological and molecular changes involved in MC activation and fibrogenesis will contribute to the development of novel approaches for the prevention and therapy of liver fibrosis.
Epithelial Cells/*physiology ; Epithelium/metabolism ; Hepatic Stellate Cells/*physiology ; Humans ; Liver/*cytology/injuries/*physiology ; Liver Cirrhosis/etiology/prevention & control ; Liver Regeneration/*physiology ; Mesenchymal Stromal Cells/physiology ; Myofibroblasts/physiology

OBJECTIVETo explore the effects of different hepatic inflow occlusion methods on liver regeneration in rats after partial hepatectomy (PH).

METHODSMale Wistar-Furth rats were randomly assigned to three groups: control group, underwent 68% hepatectomy alone; occlusion of portal triad (OPT) group, subjected to occlusion of portal triad under portal blood bypass; and occlusion of portal vein (OPV) group, subjected to occlusion of portal vein under portal blood bypass. Blood flow was occluded for 20, 30, and 40 minutes before 68% hepatectomy. According to the 7-day survival of each group, a same occlusion time T was set. Each group was divided into two subgroups (n = 8), in which animals were killed 3 and 7 days later. Liver regeneration was calculated as a percent of initial liver weight. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and Ki-67 was performed to quantify proliferating cells. In addition, functional liver volume represented by 99Tc(m)-GSA radioactivity was assessed.

RESULTSThe safe tolerance limit time was 30 minutes for OPT group and 40 minutes for OPV group. At 3 days after PH, no significant difference was observed in the regeneration rate of each group (P > 0.05). However, liver radioactive activity, PCNA labeling index, and Ki-67 index of OPV group was significantly higher than those of OPT group (P < 0.05); the latter were similar to those of control group (P > 0.05). At 7 days after PH, no significant difference was observed in all indexes among three groups (P > 0.05).

CONCLUSIONCompared with Pringle maneuver, preserving the hepatic artery flow during portal triad blood inflow occlusion can promote remnant liver regeneration early after PH.

Animals ; Hepatectomy ; methods ; Liver ; blood supply ; surgery ; Liver Regeneration ; physiology ; Male ; Postoperative Period ; Rats ; Rats, Wistar

Cloning, Molecular ; Gene Expression ; Liver ; physiology ; Liver Regeneration ; Recombinant Proteins ; genetics ; metabolism ; Yeasts

Hepatic parenchymal cells are a type of liver cells that performs important functions such as metabolism and detoxification. The contribution of hepatic parenchymal cells, bile duct cells, and hepatic stem/progenitor cells to new hepatic parenchymal cells in the process of liver injury repair has become a controversial issue due to their strong proliferation ability. Lineage tracing technology, which has emerged in the past decade as a new method for exploring the origin of cells, can trace specific type of cells and their daughter cells by labeling cells that express the specific gene and their progeny. The article reviews the current literature on the origin and contribution of hepatic parenchymal cells by this technique. About 98% of new hepatic parenchymal cells originate from the existing hepatic parenchymal cells during liver homeostasis and after acute injury. However, under conditions of severe liver injury, such as inhibition of hepatic parenchymal cell proliferation, bile duct cells (mainly liver stem/progenitor cells) become the predominant source of hepatic parenchymal cells, contributing a steady increased hepatocyte regeneration with the extension of time.
Hepatocytes/metabolism* ; Liver/metabolism* ; Bile Ducts ; Stem Cells ; Liver Regeneration/physiology* ; Cell Differentiation

In cirrhotic patients undergoing liver transplantation, reperfusion of a liver graft typically increases portal venous blood flow (PVF) because of a decrease in resistance in the liver graft to the PVF and underlying hyperdynamic splanchnic circulation, which develops due to liver cirrhosis complicated by portal hypertension and persists even after successful liver transplantation. If the liver graft has enough capacity to accommodate the increased PVF, the shear stress inflicted on the sinusoidal endothelial cells of the graft promotes hepatic regeneration; otherwise, small-for-size syndrome (SFSS) develops, leading to poor graft function and graft failure. In particular, a partial graft transplanted to patients undergoing living donor liver transplantation has less capacity to accommodate the enhanced PVF than a whole liver graft. Thus, the clinical conditions that the partial graft encounters determine either hepatic regeneration or development of SFSS. Consistent with this, this review will discuss the two conflicting effects of portal hyperperfusion (hepatic regeneration vs. portal hyperperfusion injury) on the partial grafts in cirrhotic patients suffering from hyperdynamic splanchnic circulation, in addition to normal physiology and pathophysiology of hepatic hemodynamics.
Endothelial Cells ; Hemodynamics ; Humans ; Hypertension, Portal ; Liver Cirrhosis ; Liver Regeneration ; Liver Transplantation ; Liver* ; Living Donors ; Physiology ; Regeneration* ; Reperfusion ; Splanchnic Circulation* ; Transplants*

Administering of 2-acetylaminofluorene (2-AAF) before a two-thirds partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. The objectives of this study was to examine the oval cell behaviour and associated transforming growth factor-beta1 (TGF-beta1) protein expression by combining 2-AAF with selective hepatic damage caused by PHx. We also studied the temporal relationship between TGF-beta1 expression, and proliferation and apoptosis of oval cells. Oval cells emerged from the portal areas and became more numerous with time fanning out into the periportal and midzonal hepatic parenchyma. Both smooth muscle actin (SMA) and TGF-beta1 immunostain revealed that TGF-beta1-positive cells were SMA-positive hepatic stellate cells (HSCs). Coinciding with the proliferation of oval cells, an increase expression of TGF-beta1 produced by SMA-positive HSCs was observed, thereafter apoptosis of oval cells reached its peak. This result implicated that TGF-beta1 produced by HSCs is intimately associated with proliferation and apoptosis of oval cells, and plays a role in the cessation of oval cell activation and remodeling of liver parenchyma in 2-AAF induced liver regeneration.
2-Acetylaminofluorene ; Animal ; Apoptosis/physiology* ; Hepatectomy ; Immunohistochemistry ; In Situ Nick-End Labeling ; Liver/ultrastructure ; Liver/metabolism* ; Liver/cytology ; Liver Regeneration/physiology* ; Liver Regeneration/drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/metabolism*

Animals ; Cell Differentiation ; Hepatocytes ; cytology ; Humans ; Liver Diseases ; therapy ; Liver Regeneration ; physiology ; Research ; trends ; Stem Cell Transplantation ; Stem Cells ; cytology

Partial hepatectomy (PH) endorses quiescent hepatocytes to reenter the cell cycle. The regenerating liver returns to its preresection weight after 7 days, following one or two cell division and maintains nearly its original volume after then. We focused on the inhibition of further hepatocyte proliferation, hypothesizing possible involvement of cell cycle upregulators and inhibitors. We studied protein levels in expression of cyclins, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs), and their in situ hepatic lobular distributions in partial hepatectomized rat liver. Cyclin E was expressed in the same levels in normal liver and after PH. Expression of cyclin A, not detected in normal liver, increased in following times after PH and reached a maximum at 7 day. CDK2 and 4 showed increased expression toward terminal period. Contradictory findings of cyclin A and these CDKs might play an important role in the inhibition of further cell division, although still unclear. Constitutively expressed CDK6 decreased after 1 day. p18 showed peak expression within 1 day, and p16, p21, p27 and p57 were stronger at terminal periods. During the expected period of their activity, intranuclear translocations were observed in cyclin E, p18 and p16. There was no evidence of regional distribution in hepatic lobular architecture, instead, diffuse in situ expression, corroborating synchronous event, was found.
Animal ; Cell Cycle/physiology* ; Cyclin-Dependent Kinases/metabolism ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Cyclins/metabolism* ; Cyclins/immunology ; Flow Cytometry ; Hepatectomy ; Immunoblotting ; Immunohistochemistry ; Interphase/physiology ; Liver/metabolism* ; Liver Regeneration/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; S Phase/physiology

OBJECTIVETo investigate the effects of augmenter of liver regeneration (ALR) on the proliferation of hepatocytes and hepatic tumor cells and the expression of ALR in herpatocellular carcinoma (HCC).

METHODSPrimary rat hepatocytes, QGY and HepG2 cells were cultured separately with ALR from different species. Cell proliferation was detected by their 3H-TdR uptake. The expression of ALR was examined in 9 normal hepatic tissues and 21 HCC cases using immunohistochemistry method.

RESULTSDifferent ALRs could stimulate the proliferation of HepG2 and QGY cells in a dose-dependent way in vitro, but all ALR had no influence in the proliferation of primary rat hepatocytes. The expression of ALR was absent in normal hepatic tissues, but present in all HCC hepatic tissues. However, the expression of ALR had no relationship with the differentiation and size of the carcinomas.

CONCLUSIONALR might play an important role in the occurrence and development of HCC.

Animals ; Carcinoma, Hepatocellular ; metabolism ; Hepatocytes ; metabolism ; Liver Neoplasms ; metabolism ; Liver Regeneration ; drug effects ; physiology ; Male ; Proteins ; genetics ; metabolism ; Rats ; Rats, Wistar