Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats

Assimakopoulos, Stelios F.; Tsamandas, Athanassios C.; Alexandris, Ilias H; Georgiou, Christos D.; Vagianos, Constantine; Scopa, Chrisoula D.

doi:10.4291/wjgp.v2.i6.146

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…Additionally, hepatomas that originate from spontaneously retro-differentiated hepatocytes can express AFP [ 27 , 37 , 38 ]; (c) In very extensive or chronic inflammation liver injury models, when the regenerative capacity of hepatocytes is impeded, reconstitution of the liver occurs through biliary epithelial cells (oval cells) that possess regenerative capacity with multilinear differentiation potential. Biliary epithelial cell proliferation leads to increases in AFP-specific immune expression [ 34 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furukawa et al [ 29 ] found that increased oxidative stress led to dysregulated production of adipocytokines, and that increased reactive oxygen species production from adipose tissue led to increased oxidative stress in the blood, which hazardously affected the liver, skeletal muscle, and the aorta in MS patients. Kuhlmann et al and Assimakopoulos et al observed oval cell proliferation during liver regeneration concomitant with increased AFP expression, with the mechanism being different from AFP expression in hepatocytes [ 34 , 39 ]. From this previous research and our own observations, we considered that oxidative stress and oval cell proliferation were responsible for the elevation of serum AFP levels in patients with MS.…”

Section: Discussionmentioning

confidence: 99%

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Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study

et al. 2016

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BackgroundMetabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population.MethodsA cross-sectional study was performed with 7 755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome.ResultsParticipants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides.ConclusionsThese results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study

et al. 2016

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“…When the liver is severely injured, hepatocytes may be lost through apoptosis, necrosis or reduced proliferation. Previous investigations have suggested that a hepatic progenitor cell population of oval cells are recruited to repair the damaged liver (19). Hepatic oval cells are considered to represent a stem-like cell lineage, originating from the intrahepatic bile ducts or bone marrow cells (20,21).…”

Section: Discussionmentioning

confidence: 99%

Matrine induces the hepatic differentiation of WB-F344 rat hepatic progenitor cells and inhibits Jagged 1/HES1 signaling

Yang

Wang

2016

Molecular Medicine Reports

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Matrine is a Chinese medicine, which is widely utilized for the attenuation of liver injuries and promotion of liver regeneration. It was previously observed that the in vivo administration of matrine promoted oval cell‑mediated liver regeneration in a rat model, suggesting that this compound may affect the differentiation of hepatic progenitor cells. The present study aimed to determine the mechanisms underlying this observation and to investigate the effect of matrine on the differentiation of the WB‑F344 rat hepatic progenitor cell line. Matrine was administered to rats, and rat serum was collected. WB‑F344 cells were cultured in the presence or absence of the rat serum for 24‑72 h, and the effects on cell viability and proliferation were assessed using acridine orange/propidium iodide staining and a 3‑(4,5‑dimethylthiazol‑2‑yl) ‑2,5‑diphenyltetrazolium bromide assay. The expression of albumin (ALB, a hepatocyte marker) and the notch signaling pathway ligand, Jagged 1, were assessed using immunohistochemistry and western blotting, and the mRNA transcription of ALB, Jagged 1 and hairy and enhancer of split‑1 (HES1, another notch signaling ligand) were measured using reverse transcription‑polymerase chain reaction analysis. The results showed that proliferation of the WB‑F344 cells was inhibited by matrine serum in a concentration‑ and time‑dependent manner. Matrine serum downregulated Jagged 1 and HES1, and upregulated ALB, indicating the induction of WB‑F344 cell differentiation. The effects of matrine serum were reversed by supplementing the culture medium with 0.1 mol/l parathyroid hormone, a Notch signaling pathway activator. In conclusion, matrine induced hepatic differentiation of the hepatic progenitor cells, likely by inhibiting the Jagged 1/HES1 signaling pathway.

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“…Kuhlmann et al 8 and Assimakopoulos et al 28 An increase in AFP expression during hepatocyte regeneration.…”

Section: Authorsmentioning

confidence: 99%

Elevated Serum Alpha-fetoprotein Levels in Non-alcoholic Steatohepatitis: Possible Molecular Mechanisms and Potential Clinical Significance

Wang¹,

Cui²,

Zhang³

et al. 2023

Gene Expr

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With the improvement of living standards in recent years, up to 90% of obese patients have nonalcoholic fatty liver disease (NAFLD). The number of nonalcoholic steatohepatitis (NASH)-related deaths will gradually increase, and NASH is expected to be the most common cause of liver-related deaths in the future. Therefore, there is an urgent need to find effective and reliable serum biomarkers to distinguish simple hepatic steatosis (SS) from NASH. Liver cell regeneration, oxidative stress-induced DNA methylation, and biliary epithelial cell proliferation were reported to increase serum alpha-fetoprotein (AFP) levels. AFP has long been used as a tool to monitor liver cancer. However, the function of AFP in NAFLD, especially NASH, has not been clarified. Moreover, whether an elevated AFP level indicates the occurrence of NASH or serves as a serum biomarker remains to be elucidated. The miRNA-122 pathway, DNA methylation and DNA damage, and activation of resident stem cells and/ or progenitor cells in the liver, as well as necrosis, regeneration, and repair of liver cells, may contribute to slight increases in AFP levels in the development of NASH in patients with NAFLD. Furthermore, mildly elevated AFP levels may indicate the development of NASH. This review explores the role of elevated AFP levels in the development of NASH, with a specific focus on the underlying molecular mechanisms and the clinical significance.

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Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats

Cited by 7 publications

References 41 publications

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study

Matrine induces the hepatic differentiation of WB-F344 rat hepatic progenitor cells and inhibits Jagged 1/HES1 signaling

Elevated Serum Alpha-fetoprotein Levels in Non-alcoholic Steatohepatitis: Possible Molecular Mechanisms and Potential Clinical Significance

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