Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of progenitor or stem cells in the adult liver and their potential roles in oncogenesis are unresolved issues. The study of hepatocyte progenitor cells has been limited by a lack of convenient in vivo systems allowing unequivocal cell localization and demonstration of differentiation into hepatocytes. To develop an in vivo progenitor bioassay, early (E14) fetal Fischer 344 rat hepatoblasts were transplanted into the spleen of syngeneic, weaning rats deficient in dipeptidyl peptidase IV (DPPIV) activity. The donor status of transplanted hepatoblasts was demonstrated by DPPIV expression. Localization of hepatoblasts was facilitated by the use of an ectopic site, as well as weanling recipients, which readily allowed identification of very small numbers of transplanted cells. Fetal rat hepatoblasts were demonstrated to undergo cellular differentiation along the hepatocyte lineage by acquiring glucose-6-phosphatase activity within 5 d of transplantation. A critical review of previous transplantation studies of hepatocyte progenitor cells and the role of the local microenvironment at inducing differentiation indicates that this novel bioassay should facilitate analysis of progenitor cells.
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PMID:Demonstration of differentiation in hepatocyte progenitor cells using dipeptidyl peptidase IV deficient mutant rats. 755 Apr 51

Mechanisms directing position-specific liver gene regulation are incompletely understood. To establish whether this aspect of hepatic gene expression is an inveterate phenomenon, we used transplanted hepatocytes as reporters in dipeptidyl peptidase IV-deficient F344 rats. After integration in liver parenchyma, the position of transplanted cells was shifted from periportal to perivenous areas by targeted hepatic ablations with carbon tetrachloride. In controls, transplanted cells showed greater glucose-6-phosphatase and lesser glycogen content in periportal areas. This pattern was reversed when transplanted cells shifted from periportal to perivenous areas. Transplanted hepatocytes in perivenous areas exhibited inducible cytochrome P450 activity, which was deficient in periportal hepatocytes. Moreover, cytochrome P450 activity was rapidly extinguished in activated hepatocytes when these cells were transplanted into the nonpermissive liver of suckling rat pups. In cells isolated from the normal F344 rat liver, cytochrome P450 inducibility was originally greater in perivenous hepatocytes; however, periportal cells rapidly acquired this facility in culture conditions. These findings indicate that the liver microenvironment exerts supremacy over prior differentiation state of cells in directing position-specific gene expression. Therefore, persistence of specialized hepatocellular function will require interactions with regulatory signals and substrate availability, which bears upon further analysis of liver gene regulation, including in progenitor and/or stem cells.
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PMID:Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state. 989 Sep 78

Repopulation of the cirrhotic liver with disease-resistant hepatocytes could offer novel therapies, as well as systems for biological studies. Establishing whether transplanted hepatocytes can engraft, survive, and proliferate in the cirrhotic liver is a critical demonstration. Dipeptidyl peptidase IV-deficient F344 rats were used to localize transplanted hepatocytes isolated from the liver of syngeneic normal F344 rats. Cirrhosis was induced by administration of carbon tetrachloride with phenobarbitone and these drugs were withdrawn prior to cell transplantation. Cirrhotic rats showed characteristic hepatic histology, as well as significant portosystemic shunting. When hepatocytes were transplanted via the spleen, cells were distributed immediately in periportal areas, fibrous septa, and regenerative nodules of the cirrhotic liver. Although some transplanted cells translocated into pulmonary capillaries, this was not deleterious. At 1 week, transplanted cells were fully integrated in the liver parenchyma, along with expression of glucose-6-phosphatase and glycogen as reporters of hepatic function. Transplanted cells proliferated in the liver of cirrhotic animals and survived indefinitely. At 1 year, transplanted hepatocytes formed large clusters containing several-fold more cells than normal control animals, which was in agreement with increased cell turnover in the cirrhotic rat liver. The findings indicate that the cirrhotic liver can be repopulated with functionally intact hepatocytes that are capable of proliferating. Liver repopulation using disease-resistant hepatocytes will be applicable in chronic conditions, such as viral hepatitis or Wilson's disease.
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PMID:Transplanted hepatocytes engraft, survive, and proliferate in the liver of rats with carbon tetrachloride-induced cirrhosis. 1076 23

The monoclonal antibody designated mAb Das-1, which was generated against a colon epithelial protein, reacts with the normal biliary epithelium and keratinocytes, which are among targets of tissue injury in ulcerative colitis. Moreover, mAb Das-1 reacts with abnormal cells in Barrett's esophagus and chronic cystitis profunda, as well as so-called 'oval cells' in the adult liver, which are considered oncogenic progenitor cells. To establish ontogenic regulation of mAb Das-1 reactivity, we studied 7- to 24-week-old human fetuses by immunohistochemistry. In liver, mAb Das-1 reactivity was further correlated with glycogen, dipeptidyl peptidase IV, glucose-6-phosphatase and gamma-glutamyl transpeptidase expression. mAb Das-1 reacted with cells in organs arising from the pharyngeal cleft (thymus), primitive gut (oral cavity, pharynx, lung, esophagus, stomach, biliary tree, pancreas, liver, colon), ureteric bud (renal tubules, collecting duct), mesonephros (kidney, testis), mesoderm (muscle) and elsewhere (skin, adrenal cortex). In distinction from the adult liver, mAb Das-1 staining was more pronounced in hepatoblasts compared with biliary cells. In adult tissues, however, mAb Das-1 reactivity was restricted to the colon, biliary epithelium, keratinocytes, and ciliary body. These data indicated that the mAb Das-1 recognized epitopes in fetal cells of diverse ectodermal, mesodermal and endodermal origin, compatible with sharing of lineage mechanisms in tissues. Reactivation of mAb Das-1 staining in epithelial precancerous conditions, including carcinomas arising in these organs, is compatible with oncofetal regulation of the antigen, which will facilitate analysis of cell subpopulations during organ development, regeneration and oncogenesis.
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PMID:An antigen reacting with das-1 monoclonal antibody is ontogenically regulated in diverse organs including liver and indicates sharing of developmental mechanisms among cell lineages. 1087 4

Epithelial cells in embryonic day (ED) 12.5 murine fetal liver were separated from hematopoietic cell populations using fluorescence-activated cell sorting (FACS) and were characterized by immunocytochemistry using a broad set of antibodies specific for epithelial cells (alpha-fetoprotein [AFP], albumin [ALB], pancytokeratin [PanCK], Liv2, E-cadherin, Dlk), hematopoietic/endothelial cells (Ter119, CD45, CD31), and stem/progenitor cells (c-Kit, CD34, Sca-1). AFP(+)/ALB(+) cells represented approximately 2.5% of total cells and were positive for the epithelial-specific surface markers Liv2, E-cadherin, and Dlk, but were clearly separated and distinct from hematopoietic cells (Ter119(+)/CD45(+)). Fetal liver epithelial cells (AFP(+)/E-cadherin(+)) were Sca-1(+) but showed no expression of hematopoietic stem cell markers c-Kit and CD34. These cells were enriched by FACS sorting for E-cadherin to a purity of 95% as defined by co-expression of AFP and PanCK. Purified fetal liver epithelial cells formed clusters in cell culture and differentiated along the hepatocytic lineage in the presence of dexamethasone, expressing glucose-6-phosphatase (G6P) and tyrosine amino transferase. Wild-type ED12.5 murine fetal liver cells were transplanted into adult dipeptidyl peptidase IV knockout mice and differentiated into mature hepatocytes expressing ALB, G6P, and glycogen, indicating normal biochemical function. Transplanted cells became fully incorporated into the hepatic parenchymal cords and showed up to 80% liver repopulation at 2 to 6 months after cell transplantation. In conclusion, we isolated and highly purified a population of epithelial cells from the ED12.5 mouse fetal liver that are clearly separate from hematopoietic cells and differentiate into mature, functional hepatocytes in vivo with the capacity for efficient liver repopulation. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
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PMID:Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. 1589 27

The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, rat hepatocyte clones were developed by transduction with the gene encoding the Simian virus 40 T antigen (SVT) using the human artificial minichromosome (HAC). The SVLT sequence was excised by FRT recombination. Following HAC infusion, the transduced hepatocytes express SVT, blasticidine resistance (BS), and the PGK promoter TK gene. Forty-six cell clones were obtained and at least partially characterized, as previously described, for albumin, alpha-1-antitrypsin, glucose-6-phosphatase (G6Pase), dipeptidylpeptidase 4 (Dpp4), gamma-glutamyltransferase 1 (Ggt), SVT, and beta-actin expression using RT-PCR. Clones were also assessed for albumin secretion into the culture medium using ELISA. All of the cell line secreted approximately 10 mg/dl of albumin, which is equivalent to the amount secreted by primary hepatocytes. In further experiments, this cell line will be used for transplantable cells or artificial organ using HAC. These results represent an important step toward the development of immortalized hepatocytes.
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PMID:Immortalized hepatocytes using human artificial chromosome. 1846 46