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111.
Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes 总被引:5,自引:0,他引:5
Ishikawa T Terai S Urata Y Marumoto Y Aoyama K Sakaida I Murata T Nishina H Shinoda K Uchimura S Hamamoto Y Okita K 《Cell and tissue research》2006,323(2):221-231
We have developed an in vivo mouse model, the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model, and have previously reported that transplanted GFP-positive bone marrow cells (BMCs) differentiate into hepatocytes
via hepatoblast intermediates. Here, we have investigated the growth factors that are closely related to the differentiation
of transplanted BMCs into hepatocytes, and the way that a specific growth factor affects the differentiation process in the
GFP/CCl4 model. We performed immunohistochemical analysis to identify an important growth factor in our model, viz., fibroblast growth
factor (FGF). In liver samples, the expression of FGF1 and FGF2 and of FGF receptors (FGFRs; FGFR1, FGFR2) was significantly
elevated with time after bone marrow transplantation (BMT) compared with other factors, and co-expression of GFP and FGFs
or FGFRs could be detected. We then analyzed the effect and molecular mechanism of FGF signaling on the enhancement of BMC
differentiation into hepatocytes by immunohistochemistry, immunoblotting, and microarray analysis. Treatment with recombinant
FGF (rFGF), especially rFGF2, elevated the repopulation rate of GFP-positive cells in the liver and significantly increased
the expression of both Liv2 (hepatoblast marker) and albumin (hepatocyte marker). Administration of rFGF2 at BMT also raised
serum albumin levels and improved the survival rate. Transplantation of BMCs with rFGF2 specifically activated tumor necrosis
factor-alpha (TNF-α) signaling. Thus, FGF2 facilitates the differentiation of transplanted BMCs into albumin-producing hepatocytes
via Liv2-positive hepatoblast intermediates through the activation of TNF-α signaling. Administration of FGF2 in combination
with BMT improves the liver function and prognosis of mice with CCl4-induced liver damage.
This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (nos.
13470121, 13770262, 15790348, 16390211, and 16590597) and for translational research from the Ministry of Health, Labor and
Welfare (H-trans-5). 相似文献
112.
113.
Raman spectroscopy has proven to be a very powerful technique and is currently experiencing a renaissance. In this paper, it is used to explore the interaction between doxorubicin and malignant hepatocytes in vitro. For the addition of doxorubicin, the band intensity at 1609 cm− 1, mainly assigned to CC in-plane bending mode of phenylalanine and/or tyrosine residues, increases significantly, and the intensities of the bands at 1585 and 1313 cm− 1, mainly due to the guanine bases, decrease greatly. In addition, Raman spectra are investigated at different doxorubicin concentrations, and the mean areas ratios of the band at 1450 to that at 1003 cm− 1, A1450/A1003, fluctuate according to the doxorubicin concentration increasing, which suggests that doxorubicin affects the relative content of lipid in cells. 相似文献
114.
Janie L. Baratta Anthony Ngo Bryan Lopez Natasha Kasabwalla Kenneth J. Longmuir Richard T. Robertson 《Histochemistry and cell biology》2009,131(6):713-726
The cellular organization of normal mouse liver was studied using light and electron microscopy and quantitative immunocytochemical
techniques. The general histological organization of the mouse liver is similar to livers of other mammalian species, with
a lobular organization based on the distributions of portal areas and central venules. The parenchymal hepatocytes were detected
with immunocytochemical techniques to recognize albumin or biotin containing cells. The macrophage Kupffer cells were identified
with F4-80 immunocytochemistry, Ito stellate cells were identified with GFAP immunocytochemistry, and endothelial cells were
labeled with the CD-34 antibody. Kupffer cells were labeled with intravascularly administered fluorescently labeled latex
microspheres of both large (0.5 μm) and small (0.03 μm) diameters, while endothelial cells were labeled only with small diameter
microspheres. Neither hepatocytes nor Ito stellate cells were labeled by intravascularly administered latex microspheres.
The principal fine structural features of hepatocytes and non-parenchymal cells of mouse liver are similar to those reported
for rat. Counts of immunocytochemically labeled cells with stained nuclei indicated that hepatocytes constituted approximately
52% of all labeled cells, Kupffer cells about 18%, Ito cells about 8%, and endothelial cells about 22% of all labeled cells.
Approximately, 35% of the hepatocytes contained two nuclei; none of the Kupffer or Ito cells were double nucleated. The presence
of canaliculi and a bile duct system appear similar to that reported for other species. The cellular organization of the mouse
liver is quite similar to that of other mammalian species, confirming that the mouse presents a useful animal model for studies
of liver structure and function. 相似文献
115.
Minoru Tanaka Mayuko Okabe Kaori Suzuki Yoshiko Kamiya Yuko Tsukahara Shigeru Saito Atsushi Miyajima 《Mechanisms of development》2009,126(8-9):665-676
Hepatoblasts are hepatic progenitor cells that expand and give rise to either hepatocyte or cholangiocytes during liver development. We previously reported that delta-like 1 homolog (DLK1) is expressed in the mouse liver primordium at embryonic day (E) 10.5 and that DLK1+ cells in E14.5 liver contain high proliferative and bipotential hepatoblasts. While the expression of epithelial cell adhesion molecule (EpCAM) in hepatic stem/progenitor cells has been reported, its expression profile at an early stage of liver development remains unknown. In this study, we show that EpCAM is expressed in mouse liver bud at E9.5 and that EpCAM+DLK1+ hepatoblasts form hepatic cords at the early stage of hepatogenesis. DLK1+ cells of E11.5 liver were fractionated into EpCAM+ and EpCAM− cells; one forth of EpCAM+DLK1+ cells formed a colony in vitro whereas EpCAM−DLK1+ cells rarely did it. Moreover, EpCAM+DLK1+ cells contained cells capable of forming a large colony, indicating that EpCAM+DLK1+ cells in E11.5 liver contain early hepatoblasts with high proliferation potential. Interestingly, EpCAM expression in hepatoblasts was dramatically reduced along with liver development and the colony-forming capacities of both EpCAM+DLK1+ and EpCAM−DLK1+ cells were comparable in E14.5 liver. It strongly suggested that most of mouse hepatoblasts are losing EpCAM expression at this stage. Moreover, we provide evidence that EpCAM+DLK1+ cells in E11.5 liver contain extrahepatic bile duct cells as well as hepatoblasts, while EpCAM−DLK1+ cells contain mesothelial cell precursors. Thus, the expression of EpCAM and DLK1 suggests the developmental pathways of mouse liver progenitors. 相似文献
116.
Mitochondrial metabolism depends on movement of hydrophilic metabolites through the mitochondrial outer membrane via the voltage-dependent anion channel (VDAC). Here we assessed VDAC permeability of intracellular mitochondria in cultured hepatocytes after plasma membrane permeabilization with 8 μM digitonin. Blockade of VDAC with Koenig’s polyanion inhibited uncoupled and ADP-stimulated respiration of permeabilized hepatocytes by 33% and 41%, respectively. Tenfold greater digitonin (80 μM) relieved KPA-induced inhibition and also released cytochrome c, signifying mitochondrial outer membrane permeabilization. Acute ethanol exposure also decreased respiration and accessibility of mitochondrial adenylate kinase (AK) of permeabilized hepatocytes membranes by 40% and 32%, respectively. This inhibition was reversed by high digitonin. Outer membrane permeability was independently assessed by confocal microscopy from entrapment of 3 kDa tetramethylrhodamine-conjugated dextran (RhoDex) in mitochondria of mechanically permeabilized hepatocytes. Ethanol decreased RhoDex entrapment in mitochondria by 35% of that observed in control cells. Overall, these results demonstrate that acute ethanol exposure decreases mitochondrial outer membrane permeability most likely by inhibition of VDAC. 相似文献
117.
Rebecca C. Stratton Paul E. Squires Anne K. Green 《The Journal of biological chemistry》2010,285(35):27201-27212
Rapid non-genomic effects of 17β-estradiol, the principal circulating estrogen, have been observed in a wide variety of cell types. Here we investigate rapid signaling effects of 17β-estradiol in rat hepatocytes. We show that, above a threshold concentration of 1 nm, 17β-estradiol, but not 17α-estradiol, stimulates particulate guanylyl cyclase to elevate cGMP, which through activation and plasma membrane recruitment of protein kinase G isoform Iα, stimulates plasma membrane Ca2+-ATPase-mediated Ca2+ efflux from rat hepatocytes. These effects are extremely rapid in onset and are mimicked by a membrane-impermeant 17β-estradiol-BSA conjugate, suggesting that 17β-estradiol acts at the extracellular face of the plasma membrane. We also show that 17β-estradiol binds specifically to the intact hepatocyte plasma membrane through an interaction that is competed by an excess of atrial natriuretic peptide but also shows many similarities to the pharmacological characteristics of the putative γ-adrenergic receptor. We, therefore, propose that the observed rapid signaling effects of 17β-estradiol are mediated either through the guanylyl cyclase A receptor for atrial natriuretic peptide or through the γ-adrenergic receptor, which is either itself a transmembrane guanylyl cyclase or activates a transmembrane guanylyl cyclase through cross-talk signaling. 相似文献
118.
119.
Shadi Abu-Hayyeh Pablo Martinez-Becerra Siti H. Sheikh Abdul Kadir Clare Selden Marta R. Romero Myrddin Rees Hanns-Ulrich Marschall Jose J. G. Marin Catherine Williamson 《The Journal of biological chemistry》2010,285(22):16504-16512
Sulfated progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy. ICP can be complicated by preterm labor and intrauterine death. The impact of P4-S on bile acid uptake was studied using two experimental models of hepatic uptake of bile acids, namely cultured primary human hepatocytes (PHH) and Na+-taurocholate co-transporting polypeptide (NTCP)-expressing Xenopus laevis oocytes. Two P4-S compounds, allopregnanolone-sulfate (PM4-S) and epiallopregnanolone-sulfate (PM5-S), reduced [3H]taurocholate (TC) uptake in a dose-dependent manner in PHH, with both Na+-dependent and -independent bile acid uptake systems significantly inhibited. PM5-S-mediated inhibition of TC uptake could be reversed by increasing the TC concentration against a fixed PM5-S dose indicating competitive inhibition. Experiments using NTCP-expressing Xenopus oocytes confirmed that PM4-S/PM5-S are capable of competitively inhibiting NTCP-mediated uptake of [3H]TC. Total serum PM4-S + PM5-S levels were measured in non-pregnant and third trimester pregnant women using liquid chromatography-electrospray tandem mass spectrometry and were increased in pregnant women, at levels capable of inhibiting TC uptake. In conclusion, pregnancy levels of P4-S can inhibit Na+-dependent and -independent influx of taurocholate in PHH and cause competitive inhibition of NTCP-mediated uptake of taurocholate in Xenopus oocytes. 相似文献
120.