Prostaglandin E2 and rat liver regeneration

Tsujii, Hiroyuki; Okamoto, Yasuyuki; Kikuchi, Eiryo; Matsumoto, Masami; Nakano, Hiroshi

doi:10.1016/0016-5085(93)90725-r

Cited by 78 publications

(51 citation statements)

References 11 publications

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“…The EP2 transcript was detected in the liver, in which no signals for the EP4 receptor were detected. PGE2 was reported to be involved in liver regeneration [31], and PGE2 and other cAMP-elevating agents can induce the expression of hepatocyte growth factor [32]. EP2 might be involved in these actions of PGE2.…”

Section: Resultsmentioning

confidence: 99%

The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis

et al. 1995

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A functional cDNA clone for the mouse prostaglandin I PG) E receptor EP 2 subtype was isolated from a mouse cDNA library. The mouse EP2 receptor consists of 362 amino acid residues with seven putative transmembrane domains. [3H]PGE2 bound specifically to the membrane of Chinese hamster ovary tells stably expressing the cloned receptor. This binding was displaced by unlabeled prostanoids in the order of PGEz = I'GEt >> iloprost, a stable PGI 2 agonist > PGFz~ > PGDz. Binding was also inhibited by butaprost (an EP2 agonist) and to a lesser extent by M&B 28767 (an EP 3 agonist), but not by sulprostone (an EP~ and EP 3 agonis0 or SC-19220 (an EP~ antagonist). PGE 2 and butaprost increased the cAMP level in the Chinese hamster ovary cells in a concentration-dependent manner. Northvrn blot analysis revealed that EP 2 mRNA is expressed most abundantly in the uterus, followed by the spleen, lung, thymus, ileum, liver, and stomach.

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Section: Resultsmentioning

confidence: 99%

The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis

et al. 1995

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“…We measured intracellular basal cAMP levels (a key regulatory determinant of cellular proliferation including ductal hyperplasia) 5,36,37 in purified cholangiocytes from normal or BDL rats, which immediately after BDL, were treated with NaCl-or RAMH for 1 week. After purification, cholangiocytes were incubated for 1 h at 371C to restore surface proteins damaged by treatment with proteolytic enzymes.…”

Section: Evaluation Of Cholangiocyte Proliferation and Camp Levelsmentioning

confidence: 99%

H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway

Francis

Franchitto

Ueno

et al. 2007

Laboratory Investigation

152

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Histamine regulates many functions by binding to four histamine G-coupled receptor proteins (H1R, H2R, H3R and H4R). As H3R exerts their effects by coupling to Ga i/o proteins reducing adenosine 3 0 , 5 0 -monophosphate (cAMP) levels (a key player in the modulation of cholangiocyte hyperplasia/damage), we evaluated the role of H3R in the regulation of biliary growth. We posed the following questions: (1) Do cholangiocytes express H3R? (2) Does in vivo administration of (R)-(a)-(À)-methylhistamine dihydrobromide (RAMH) (H3R agonist), thioperamide maleate (H3R antagonist) or histamine, in the absence/presence of thioperamide maleate, to bile duct ligated (BDL) rats regulate cholangiocyte proliferation? and (3) Does RAMH inhibit cholangiocyte proliferation by downregulation of cAMP-dependent phosphorylation of protein kinase A (PKA)/extracellular signal-regulated kinase 1/2 (ERK1/2)/ets-like gene-1 (Elk-1)? The expression of H3R was evaluated in liver sections by immunohistochemistry and immunofluorescence, and by real-time PCR in cholangiocyte RNA from normal and BDL rats. BDL rats (immediately after BDL) were treated daily with RAMH, thioperamide maleate or histamine in the absence/presence of thioperamide maleate for 1 week. Following in vivo treatment of BDL rats with RAMH for 1 week, and in vitro stimulation of BDL cholangiocytes with RAMH, we evaluated cholangiocyte proliferation, cAMP levels and PKA, ERK1/2 and Elk-1 phosphorylation. Cholangiocytes from normal and BDL rats express H3R. The expression of H3R mRNA increased in BDL compared to normal cholangiocytes. Histamine decreased cholangiocyte growth of BDL rats to a lower extent than that observed in BDL RAMH-treated rats; histamine-induced inhibition of cholangiocyte growth was partly blocked by thioperamide maleate. In BDL rats treated with thioperamide maleate, cholangiocyte hyperplasia was slightly higher than that of BDL rats. In vitro, RAMH inhibited the proliferation of BDL cholangiocytes. RAMH inhibition of cholangiocyte growth was associated with decreased cAMP levels and PKA/ERK1/2/Elk-1 phosphorylation. Downregulation of cAMP-dependent PKA/ERK1/2/Elk-1 phosphorylation (by activation of H3R) is important in the inhibition of cholangiocyte growth in liver diseases.

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“…1 Several observations have suggested that prostaglandins (PGs) may be involved in growth regulation during liver regeneration. 2,3 These compounds are synthesized from arachidonic acid by the action of cyclooxygenases COX-1 and COX-2. The former is expressed constitutively in most tissues, whereas the latter is highly inducible.…”

mentioning

confidence: 99%

“…[6][7][8] COX-2 and PGE 2 synthesis are upregulated soon after partial hepatectomy (PH), with peaks at 3 and 10 hours after operation. 3,9 Recently, liver regenerative response after PH in rodents was reported to be blocked by administration of a COX-2-specific inhibitor, 10,11 indicating the critical role of PGs during the early phase of liver regeneration. PGs display hepatoprotective activities and are also able to modulate the expression of cytokines and growth factors in other tissue systems.…”

mentioning

confidence: 99%

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

et al. 2005

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Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis. (HEPATOLOGY 2005;41:460-469.)

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Prostaglandin E2 and rat liver regeneration

Cited by 78 publications

References 11 publications

The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis

The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis

H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

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Prostaglandin E2 and rat liver regeneration

Cited by 78 publications

References 11 publications

The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and Northern blot analysis

The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and Northern blot analysis

H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

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The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis

The mouse prostaglandin E receptor EP₂ subtype: cloning, expression, and Northern blot analysis