Somatostatin suppresses endothelin-1–induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1

Reynaert, Hendrik; Vaeyens, Freya; Qin, Hongjiu; Hellemans, Karine; Chatterjee, Nirjhar; Winand, Dominique; Quartier, Erik; Schuit, Frans; Urbain, Daniël; Kumar, Ujendra; Patel, Yogesh C.; Geerts, Albert

doi:10.1053/gast.2001.27971

Cited by 62 publications

(74 citation statements)

References 82 publications

(113 reference statements)

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“…(14) In rats, sstr have been shown to be expressed in activated hepatic stellate cells in CCl 4 -treated rats (15) and low levels of sstr2 mRNA were present in normal liver and hepatoma.…”

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confidence: 99%

“…(10) It was recently shown that human HCC express sstr, (12) mainly sstr2, (13) sstr3, and sstr5. (14) In rats, sstr have been shown to be expressed in activated hepatic stellate cells in CCl 4 -treated rats (15) and low levels of sstr2 mRNA were present in normal liver and hepatoma. (16) Somatostatin analogs also exert indirect antitumor activity mainly by inhibiting tumoral neo-angiogenesis (17) and inhibition of growth factor release.…”

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confidence: 99%

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Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

et al. 2007

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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2-acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin-dependent kinase inhibitor p27 kip1 compared to the non-treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two-step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC. (Cancer Sci 2007; 98: 1831-1839) H CC represents a major public health problem. Its incidence is in constant progression, with 2-5 new cases per 100 000 inhabitants/year in western countries and more than 20 per 100 000 inhabitants/year in Asia.(1,2) Curative treatment can only be proposed in 10-20% of cases.The main risk factors of HCC development are cirrhosis and hepatitis B and C that induce genetic alterations leading to preneoplastic, then neoplastic changes. The persistence of infection and/or cirrhosis often leads to tumoral relapse after surgical resection, observed in approximately 20% per year. Therefore, chemoprevention could play an important role in the therapeutic strategy of this disease.In experimental carcinogenesis, preneoplastic foci of altered hepatocytes emerge weeks or months before the appearance of hepatocellular adenomas and HCC.(3) Similar progression has been described in human hepatocarcinogenesis.(4) This fact has led to the development of a number of in vivo systems to study early neoplasia in rat liver.(5) The initiation-promotion or two-stage model of cancer development mimics the early events of the latent period of human carcinogenesis. The initiation stage of cancer development can be produced in rat liver by injection of DEN, (6) a carcinogen that causes DNA ethylation and mutagenesis.(7) Furthermore, DEN has been shown to induce tumors in rodents that closely mimic a subclass of human HCC. Somatostatin analogs (octreotide and lanreotide) are molecules that are widely...

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“…(14) In rats, sstr have been shown to be expressed in activated hepatic stellate cells in CCl 4 -treated rats (15) and low levels of sstr2 mRNA were present in normal liver and hepatoma.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

et al. 2007

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“…In 2001 Reynaert et al [16] demonstrated that HSCs expressed SSTR 1 , SSTR 2 and SSTR 3 during their activation. Therefore, it is reasonable to deduce that somatostatin may play a negative regulatory role in the activation of HSCs via paracrine route.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and proapoptotic effects of somatostatin on activated hepatic stellate cells

Pan¹,

Li²,

Lu³

et al. 2004

WJG

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AIM:To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS:HSCs isolated from the livers of adult SpragueDawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ et hid ium br omi de flu ores cen t s tai nin g, ter min al deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis. RESULTS:Somatostatin at the concentration of 10 -6

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“…Contraction of liver MFs was examined as previously described (8,14). In brief, collagen gels were prepared by mixing 70% type I collagen from porcine tendon (Nitta Gelatin, Osaka), 20% 5 × DMEM and 10% 0.05 N NaOH under ice-cold conditions (final collagen concentration, 2.1 mg/ml).…”

Section: Collagen Gel Contraction Assaymentioning

confidence: 99%

Relaxant Effect of Prostaglandin D2–Receptor DP Agonist on Liver Myofibroblast Contraction

et al. 2011

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Abstract. Increased intrahepatic resistance causes portal hypertension in cirrhosis. Liver myofibroblasts (MFs) are now regarded as the principle cells involved in sinusoidal blood flow regulation. Many other prostaglandin-receptor agonists have been reported to regulate liver MF contraction, but the role of the prostaglandin D 2 -receptor DP is unknown. In this study, we investigated the effect of a synthetic agonist of prostanoid DP receptor, BW245C, on contractile properties of primary rat liver MFs. Collagen gel contraction assay revealed that BW245C alone (1 and 10 μM) did not induce contraction but induced cell relaxation. Pretreatment with BW245C (10 μM, 30 min) attenuated bradykinin (100 nM)-induced liver MF contraction. Elevation of [Ca 2+ ] i induced by bradykinin (100 nM) was partially suppressed by BW245C pretreatment (10 μM, 3 min). BW245C (1 and 10 μM) significantly increased intracellular cAMP level in a dose-dependent manner. Pretreatment with forskolin (30 -300 nM, 30 min) and dibutyryl-cAMP (3 -30 μM, 30 min) significantly reduced bradykinin-induced contraction. Furthermore, a protein kinase A (PKA) inhibitor KT5720 (10 nM to 1 μM, 30 min) blocked the relaxant effect of BW245C. These results suggest that prostanoid DP receptor agonism inhibits bradykinin-induced [Ca 2+ ] i elevation and contraction through cAMP-PKA signal activation in rat liver MFs.

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Somatostatin suppresses endothelin-1–induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1

Cited by 62 publications

References 82 publications

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

Antiproliferative and proapoptotic effects of somatostatin on activated hepatic stellate cells

Relaxant Effect of Prostaglandin D2–Receptor DP Agonist on Liver Myofibroblast Contraction

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