The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver

Díaz-Gil, Juan José; Majano, Pedro L.; López–Cabrera, Manuel; Sánchez-López, Vicente; Rúa, Carmen; Machı́n, C; Trilla, Carolina; García-Cañero, R.; Moreno–Otero, Ricardo

doi:10.1016/s0168-8278(03)00030-8

Cited by 14 publications

(23 citation statements)

References 32 publications

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“…Other studies have demonstrated that ligand activation of PPARβ/δ can inhibit cell proliferation by causing a block in mitosis (Zhu et al 2012). TNFα is a mitogen in the liver (Diaz-Gil et al 2003) and has been strongly linked to the development of hepatocellular carcinoma (Knight et al 2000; Park et al 2010). TNFα secreted from activated Kupffer cells can cause activation of NF-κB in hepatocytes and promote liver cancer in a cholestatic hepatitis model, and treatment with TNFα neutralizing antibodies prevents tumor progression in this model (Pikarsky et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

Balandaram

Kramer

Kang³

et al. 2016

Toxicology

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Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits steatosis and inflammation, known risk factors for liver cancer. In this study, the effect of ligand activation of PPARβ/δ in modulating liver tumorigenesis in transgenic hepatitis B virus (HBV) mice was examined. Activation of PPARβ/δ in HBV mice reduced steatosis, the average number of liver foci, and tumor multiplicity. Reduced expression of hepatic CYCLIN D1 and c-MYC, tumor necrosis factor alpha (Tnfa) mRNA, serum levels of alanine aminotransaminase, and an increase in apoptotic signaling was also observed following ligand activation of PPARβ/δ in HBV mice compared to controls. Inhibition of Tnfa mRNA expression was not observed in wild-type hepatocytes. Ligand activation of PPARβ/δ inhibited lipopolysaccharide (LPS)-induced mRNA expression of Tnfa in wild-type, but not in Pparβ/δ-null Kupffer cells. Interestingly, LPS-induced expression of Tnfa mRNA was also inhibited in Kupffer cells from a transgenic mouse line that expressed a DNA binding mutant form of PPARβ/δ compared to controls. Combined, these results suggest that ligand activation of PPARβ/δ attenuates hepatic tumorigenesis in HBV transgenic mice by inhibiting steatosis and cell proliferation, enhancing hepatocyte apoptosis, and modulating anti-inflammatory activity in Kupffer cells.

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Section: Discussionmentioning

confidence: 99%

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

Balandaram

Kramer

Kang³

et al. 2016

Toxicology

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“…It is known that fibrosis induced by excessive collagen deposition influences arterial responses to vasodilators by limiting the expansion of the vessel wall [11]. Moreover, the fact that the first target for LGF action in liver is the endothelium [18], does not exclude the possibility that the positive effect of LGF on vasodilatation might be partially due to an enhancement of vasoactive endothelial factors. In studies related to this concept, other authors have detected two specific receptors for ''modified albumin'' (albumin with some ligand bonds) in endothelial cells [36,37], that resemble LGF, an albumin -bilirubin complex [13].…”

Section: Discussionmentioning

confidence: 99%

“…In a model of Cl 4 C-induced cirrhosis induced in rats, LGF injection decreased total liver collagen, restored partial architectural integrity, necrotic tissue and serum enzymes, reducing ascites and improving hemodynamics [17]. Díaz-Gil has recently demonstrated that the first targets of LGF in liver are the endothelial cells around portal spaces, which secrete TNF-a, initiating the mitogenic pathway [18]. It is worth noting that, in endothelial cells in vitro, LGF acts at a very low concentration (5 pg/ml) [18], much lower than that required for the hepatocyte growth factor (HGF) to act on the same cells.…”

Section: Introductionmentioning

confidence: 99%

“…Díaz-Gil has recently demonstrated that the first targets of LGF in liver are the endothelial cells around portal spaces, which secrete TNF-a, initiating the mitogenic pathway [18]. It is worth noting that, in endothelial cells in vitro, LGF acts at a very low concentration (5 pg/ml) [18], much lower than that required for the hepatocyte growth factor (HGF) to act on the same cells. HGF, another growth factor, the chemical structure of which is different from that of LGF, is active in the ng/ml range [19].…”

Section: Introductionmentioning

confidence: 99%

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Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure

Somoza¹,

Abderrahim²,

González³

et al. 2006

Cardiovascular Research

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“…The first targets of LGF in liver are portal vein endothelial cells, which secrete tumor necrosis factor-a (TNF-a), initiating the mitogenic pathway (Díaz-Gil et al 2003). Moreover, LGF stimulates the synthesis of vascular endothelial growth factor (VEGF) and its receptors in testis (Martín-Hidalgo et al 2007).…”

mentioning

confidence: 99%

Mobilization of Neural Stem Cells and Generation of New Neurons in 6-OHDA–lesioned Rats by Intracerebroventricular Infusion of Liver Growth Factor

Gonzalo‐Gobernado

Reimers

Herranz

et al. 2009

J Histochem Cytochem.

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S U M M A R Y Neural stem cells with self-renewal and multilineage potential persist in the subventricular zone of the adult mammalian forebrain. These cells remain relatively quiescent but, under certain conditions, can be stimulated, giving rise to new neurons. Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and is useful for neuroregenerative therapies. The aim of this study was to investigate the potential neurogenic activity of LGF in the 6-hydroxydopamine rat model of Parkinson's disease. Proliferation was significantly increased in the subventricular zone and denervated striatum of rats receiving ICV LGF infusions, and 25% of the proliferating cells were doublecortin-positive neurons. Doublecortin-positive cells with the morphology of migrating neuroblasts were also observed in the dorsal and ventral regions of the striatum of LGF-infused animals. Moreover, some newly generated cells were neuronal nuclei-positive mature neurons.LGF also stimulated microglia and induced astrogliosis, both phenomena associated with generation and migration of new neurons in the adult brain. In summary, our study shows that LGF stimulates neurogenesis when applied intraventricularly in 6-hydroxydopamine-lesioned rats. Considering that this factor also promotes neuronal migration into damaged tissue, we propose LGF as a novel factor useful for neuronal replacement in neurodegenerative diseases. (J Histochem Cytochem 57:491-502, 2009)

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The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver

Cited by 14 publications

References 32 publications

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure

Mobilization of Neural Stem Cells and Generation of New Neurons in 6-OHDA–lesioned Rats by Intracerebroventricular Infusion of Liver Growth Factor

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