Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver

被引:35
作者
Gupta, S
Rajvanshi, P
Malhi, H
Slehria, S
Sokhi, RP
Vasa, SRG
Dabeva, M
Shafritz, DA
Kerr, A
机构
[1] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Comprehens Canc Res Ctr, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[4] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[5] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[6] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10461 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2000年 / 279卷 / 04期
关键词
hepatocyte; ischemia; injury; gene expression; vasodilatation;
D O I
10.1152/ajpgi.2000.279.4.G815
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Cell transplantation into hepatic sinusoids, which is necessary for liver repopulation, could cause hepatic ischemia. To examine the effects of cell transplantation on host hepatocytes, we transplanted Fisher 344 rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. Within 24 h of cell transplantation, areas of ischemic necrosis, along with transient disruption of gap junctions, appeared in the liver. Moreover, host hepatocytes expressed gamma-glutamyl transpeptidase (GGT) extensively, which was observed even 2 years after cell transplantation. GGT expression was not associated with alpha-fetoprotein activation, which is present in progenitor cells. Increased GGT expression was apparent after transplantation of nonparenchymal cells and latex beads but not after injection of saline, fragmented hepatocytes, hepatocyte growth factor, or turpentine. Some host hepatocytes exhibited apoptosis, as well as DNA synthesis, between 24 and 48 h after cell transplantation. Changes in gap junctions, GGT expression, DNA synthesis, and apoptosis after cell transplantation were prevented by vasodilators. The findings indicated the onset of ischemic liver injury after cell transplantation. These hepatic perturbations must be considered when transplanted cells are utilized as reporters for biological studies.
引用
收藏
页码:G815 / G826
页数:12
相关论文
共 52 条
  • [1] ANDERSON ME, 1985, CRC HDB METHODS OXYG, P317
  • [2] BEER DG, 1986, CANCER RES, V46, P2435
  • [3] HETEROGENEOUS LOBULAR DISTRIBUTION OF HEPATOCYTES EXPRESSING ACUTE-PHASE GENES DURING THE ACUTE INFLAMMATORY REACTION
    BERNUAU, D
    LEGRES, L
    LAMRI, Y
    GIUILY, N
    FEY, G
    FELDMANN, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 170 (01) : 349 - 354
  • [4] BONE SN, 1985, CANCER RES, V45, P1222
  • [5] BROUILLET A, 1994, J BIOL CHEM, V269, P14878
  • [6] Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice
    Cressman, DE
    Greenbaum, LE
    DeAngelis, RA
    Ciliberto, G
    Furth, EE
    Poli, V
    Taub, R
    [J]. SCIENCE, 1996, 274 (5291) : 1379 - 1383
  • [7] Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver
    Dabeva, MD
    Hwang, SG
    Vasa, SRG
    Hurston, E
    Novikoff, PM
    Hixson, DC
    Gupta, S
    Shafritz, DA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) : 7356 - 7361
  • [8] DABEVA MD, 1993, AM J PATHOL, V143, P1606
  • [9] TRIIODOTHYRONINE DECREASES GAMMA-GLUTAMYL-TRANSPEPTIDASE EXPRESSION IN CULTURED RAT HEPATOCYTES
    DEMORI, I
    BOTTAZZI, C
    FUGASSA, E
    [J]. HORMONE AND METABOLIC RESEARCH, 1995, 27 (05) : 221 - 225
  • [10] MODULATION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE IN NORMAL RAT HEPATOCYTES IN CULTURE BY CELL-DENSITY, EPIDERMAL GROWTH-FACTOR AND AGENTS WHICH ALTER CELL-DIFFERENTIATION
    EDWARDS, AM
    LUCAS, CM
    BADDAMS, HM
    [J]. CARCINOGENESIS, 1987, 8 (12) : 1837 - 1842