Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

Gao, Cuihua; Jokerst, Rodney; Gondipalli, Prathima; Cai, Shi Rong; Kennedy, Susan; Flye, M. Wayne; Ponder, Katherine P.

doi:10.1002/hep.510300602

Cited by 36 publications

(41 citation statements)

References 59 publications

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“…This is consistent with a previous report that HGF stimulates phosphorylation of JNK and ERK1/2 and AP-1 DNA-binding activity in hepatocytes. 33 A study using SHP-null mice suggested that SHP itself may be a component of the JNK-signaling cascade 34 and that the SHP promoter is transactivated by c-Jun. 29,35 Moreover, our recent study revealed that JNK can phosphorylate HNF4␣ and that c-Jun interacts with HNF4␣ to interfere with HNF4␣ recruitment of PGC-1␣ to CYP7A1 chromatin, thereby leading to repression of CYP7A1 expression.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

et al. 2007

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B ile acids are physiological detergents that facilitate absorption, transport, and distribution of sterols and lipid-soluble vitamins and disposal of toxic metabolites and xenobiotics. Bile acid synthesis and cholesterol 7␣-hydroxylase (CYP7A1) 2 gene transcription are inhibited by bile acids returning to the liver via enterohepatic circulation of bile acids. 1 Because bile acids are amphipathic molecules that function as powerful detergents, their concentrations in hepatocytes have to be tightly regulated to prevent cell damage. 2 Bile acids are also signaling molecules that activate nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor, and vitamin D3 receptor and play important roles in the regulation of bile acid synthesis, cholesterol metabolism, and drug metabolism. 2 It has been reported that bile acid synthesis and CYP7A1 activity are suppressed after partial hepatectomy and during liver regeneration in animals and human patients. [3][4][5] The increase of bile acids in the remaining hepatocytes after partial hepatectomy and in the early stage of liver regeneration and injury inhibits bile acid synthesis and increases bile acid excretion to protect the liver from accumulating toxic bile acids. A recent study showed that bile acids and FXR are involved in liver regeneration in mice, as FXR-null mice had a lower rate of liver regeneration. 6 However, the molecular mechanism underlying the bile acid effect on liver regeneration remains unclear. Abbreviations: CBP, cAMP response element binding protein

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Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

et al. 2007

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“…The agarose beads were resuspended in Laemmli sample buffer separated on SDS-PAGE, and analyzed by protein blot using anti-RhoA or Rac1 antibodies. Treatment of mTEC with hepatocyte growth factor (HGF) purified from HeLa cells infected with an HGF adenovirus vector (Gao et al, 1999) (kindly provided by Kathy Ponder, Washington University) was used as a control for Rac1 activation (Wells et al, 2005). An aliquot of lysate retained prior to pull-down assay was subjected to immunoblotting to determine total Rho or Rac1.…”

Section: Gtpase Activation Assaysmentioning

confidence: 99%

RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1

Pan

You

Huang

et al. 2007

Journal of Cell Science

191

176

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Programs that direct cellular differentiation are dependent on the strict temporal expression of regulatory factors that can be provided by Rho GTPases. Ciliogenesis is a complex sequence of events involving the generation and docking of basal bodies at the apical membrane, followed by ciliary axoneme generation. Although a cilia proteome has been assembled, programs that direct ciliated cell differentiation are not well established, particularly in mammalian systems. Using mouse primary culture airway epithelial cells, we identified a critical stage of ciliogenesis requiring the temporal establishment of an apical web-like structure of actin for basal body docking and subsequent axoneme growth. Apical web formation and basal body docking were prevented by interruption of actin remodeling and were dependent on RhoA activation. Additional evidence for this program was provided by analysis of Foxj1-null mice that failed to dock basal bodies and lacked apical actin. Foxj1 expression coincided with actin web formation, activated RhoA and RhoB, and persisted despite RhoA inhibition, suggesting that Foxj1 promoted RhoA during ciliogenesis. Apical ezrin localization was also dependent on Foxj1, actin remodeling, and RhoA, but was not critical for ciliogenesis. Thus, temporal Foxj1 and RhoA activity are essential regulatory events for cytoskeletal remodeling during mammalian ciliogenesis.

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“…Recombinant human HGF was purified from 293-N3S cells as detailed previously 46 and stored at Ϫ70°C in phosphate-buffered saline (PBS) (137 mM NaCl, 2.7 mM KCl, 10.1 mM Na 2 HPO 4 , and 1.8 mM KH 2 PO4, pH 7.4).…”

Section: Reagentsmentioning

confidence: 99%

Neonatal or hepatocyte growth factor–potentiated adult gene therapy with a retroviral vector results in therapeutic levels of canine factor IX for hemophilia B

Gao

Sands

et al. 2003

Blood

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Hemophilia B is a bleeding disorder resulting from factor IX (FIX) deficiency that might be treated with gene therapy. Neonatal delivery would correct the disease sooner than would transfer into adults, and could reduce immunological responses. Neonatal mice were injected intravenously with a Moloney murine leukemia virus-based retroviral vector (RV) expressing canine FIX (cFIX). They achieved 150% to 280% of normal cFIX antigen levels in plasma (100% is 5 g/ mL), which was functional in vitro and in vivo. Three newborn hemophilia B dogs that were injected intravenously with RV achieved 12% to 36% of normal cFIX antigen levels, which improved coagulation tests. Only one mild bleed has occurred during 14 total months of evaluation. This is the first demonstration of prolonged expression after neonatal gene therapy for hemophilia B in mice or dogs. Most animals failed to make antibodies to cFIX, demonstrating that neonatal gene transfer may induce tolerance. Although hepatocytes from newborns replicate, those from adults do not. Adult mice therefore received hepatocyte growth factor to induce hepatocyte replication prior to intravenous injection of RV. This resulted in expression of 35% of normal cFIX antigen levels for 11 months, although all mice produced anti-cFIX antibodies. This is the first demonstration that high levels of FIX activity can be achieved with an RV in adults without a partial hepatectomy to induce hepatocyte replication. We conclude that RV-mediated hepatic gene therapy is effective for treating hemophilia B in mice and dogs, although the immune system may complicate gene transfer in adults. IntroductionHemophilia B is a sex-linked disorder due to deficiency of factor IX (FIX) activity that affects 1 in 30 000 males. 1 Hepatic gene therapy could result in the continuous secretion of FIX into the blood and improve bleeding symptoms. Achieving more than 10% of normal activity should prevent most spontaneous bleeds, whereas 1% of normal activity should reduce, but not prevent, bleeding. There has been recent success in using hepatic gene therapy to express therapeutic levels of FIX in mice. 2 For example, lentiviral vectors resulted in FIX antigen levels that were 2% to 7% of normal 3,4 ; adeno-associated virus (AAV) vectors resulted in levels that were 10% to 40% of normal [5][6][7][8][9] or 400% of normal 10 ; adenoviral vectors resulted in levels that were 8% of normal 11 or 60% to 4100% of normal [12][13][14][15][16] ; and plasmids resulted in levels that were 7% to 80% of normal. [17][18][19] In addition, intramuscular injection of AAV vectors resulted in 3% to 7% of normal 5,20,21 or 1000% of normal levels, 22 whereas other nonhepatic approaches generally result in lower long-term expression. 2 Gene therapy appears to be less efficacious in large-animal models than in mice. In some cases, lower expression was obtained despite the use of a dose of vector per body weight similar to that used in mice, although in other cases lower expression could be attributed at least in part to the use of ...

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Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity

Cited by 36 publications

References 59 publications

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes

RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1

Neonatal or hepatocyte growth factor–potentiated adult gene therapy with a retroviral vector results in therapeutic levels of canine factor IX for hemophilia B

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