Recovery of the Cell Cycle Inhibition in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mtext>CCl</mml:mtext></mml:mrow><mml:mn>4</mml:mn></mml:msub></mml:mrow></mml:math>-Induced Cirrhosis by the Adenosine Derivative IFC-305

Sánchez, Victoria Chagoya de; Martínez-Pérez, Lidia; Hernández‐Muñoz, Rolando; Velasco-Loyden, Gabriela

doi:10.1155/2012/212530

Cited by 15 publications

(21 citation statements)

References 43 publications

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“…Besides, decreased fibrosis was evident in response to IFC-305 treatment, accelerating fibrosis resolution, leaving only 4% of fibrotic area, while increasing parenchymal liver area from 87 to 90%, and collagen was decreased to half-level as compared to saline-treated rats. This improvement in liver architecture was in accordance with liver physiological amelioration; IFC-305 reduced significantly bilirubin and serum transaminase activities [17], and ATP levels were equivalent to those of healthy liver [34], corroborating that IFC-305 presents the same hepatoprotective properties reverting cirrhosis than adenosine but with a lower dose.…”

Section: Biochemical and Physiological Alteration Of Liver During Cirsupporting

confidence: 57%

“…Liver has a well-known capability to regenerate after resection [35]; the severity of liver fibrosis is considered to be related with impaired regenerative capacity, suggesting the arrest of cell cycle [36]. The fibrogenesis process is accompanied by energetic imbalance as well as oxidative damage generated by oxygen species that could result in chromosomal instability, which induces injury in the check points of the cellular cycle triggering an impaired regenerative capacity [34].…”

Section: Cell Cycle Inhibition During Cirrhosis and Its Recovery By Imentioning

confidence: 99%

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Molecular and Cellular Aspects of Cirrhosis and How an Adenosine Derivative Could Revert Fibrosis

Rodríguez‐Aguilera¹,

Vaca²,

Guerrero‐Celis³

et al. 2019

Liver Cirrhosis - Debates and Current Challenges

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Hepatic fibrosis occurs in response to persistent liver damage and is characterized by an excessive accumulation of extracellular matrix. When the damage is prolonged, there is a chronic inflammation and persistent hepatic fibrosis eventually leads to cirrhosis, where in addition to the scar, there is an important vascular remodeling associated with portal hypertension and, if decompensated, leads to death or can develop hepatocellular carcinoma. We have been studying the pharmacologic functions of adenosine, finding that a derivative of this nucleoside, IFC-305, shows hepatoprotective effects in a CCl 4-induced rat cirrhosis model where it reverses liver fibrosis through modulation of fibrosis-related genes and by ameliorating hepatic function. Furthermore, this compound has the property to rescue cell cycle inhibition in vivo, prevents hepatic stellate cell activation, modulates antiinflammatory macrophage polarization, and favors a chromatin context that could decrease the genomic instability and characteristics of cirrhosis, enabling the recovery of gene expression profile. Here we show results that contribute to the comprehension of molecular and cellular mechanism of cirrhosis, give the opportunity to suggest biomarkers to the early diagnostic of this pathology, and constitute the fundaments to suggest IFC-305 as a coadjuvant for treatment of this disease.

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Section: Biochemical and Physiological Alteration Of Liver During Cirsupporting

confidence: 57%

Section: Cell Cycle Inhibition During Cirrhosis and Its Recovery By Imentioning

confidence: 99%

Molecular and Cellular Aspects of Cirrhosis and How an Adenosine Derivative Could Revert Fibrosis

Rodríguez‐Aguilera¹,

Vaca²,

Guerrero‐Celis³

et al. 2019

Liver Cirrhosis - Debates and Current Challenges

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“…2). From those studies multiple mechanisms have been suggested to play a role in in vivo liver amelioration [97], such as: immunomodulation [56,98] (as discussed above); apoptosis of HeSCs [99]; inhibition of HeSC activation and/or their deactivation [76,100]; protective effects on hepatic cells [100][101][102][103] (see above), and restoration or induction of hepatic cell proliferation [76,84,103,104] (Fig. 2).…”

Section: Mechanisms Involved In Msc-mediated Liver Fibrosis/cirrhosismentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Fiore

Mazzolini

Aquino

2015

Stem Cell Rev and Rep

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Mesenchymal stem/stromal cells (MSCs) are progenitors which share plastic-adherence capacity and cell surface markers but have different properties according to their cell and tissue sources and to culture conditions applied. Many recent publications suggest that MSCs can differentiate into hepatic-like cells, which can be a consequence of either a positive selection of rare in vivo pluripotent cells or of the original plasticity of some cells contributing to MSC cultures. A possible role of MSCs in hereditary transmission of obesity and/or diabetes as well as properties of MSCs regarding immunomodulation, cell fusion and exosome release capacities are discussed according to recent literature. Limitations in methods used to track MSCs in vivo especially in the context of liver cirrhosis are addressed as well as strategies explored to enhance their migratory, survival and proliferation properties, which are known to be relevant for their future clinical use. Current knowledge regarding mechanisms involved in liver cirrhosis amelioration mediated by naïve and genetically modified MSCs as well as the effects of applying preconditioning and combined strategies to improve their therapeutic effects are evaluated. Finally, first reports of GMP guidelines and biosafety issues in MSCs applications are discussed.

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“…Previously, we demonstrated in this animal model that treatment with IFC-305, an adenosine derivative, reverses liver fibrosis and ameliorates hepatic function . At the cellular level, it prevents HSC activation in vivo and in vitro Velasco-Loyden et al, 2010], promotes recovery of the cell cycle inhibition [Chagoya de Sanchez et al, 2012], and reestablishes the expression of around 150 genes deregulated in cirrhosis, among them Col1a1 and Pparg .…”

mentioning

confidence: 99%

Epigenetic Effects of an Adenosine Derivative in a Wistar Rat Model of Liver Cirrhosis

Rodríguez‐Aguilera¹,

Guerrero‐Hernández²,

Pérez‐Molina³

et al. 2017

J of Cellular Biochemistry

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The pathological characteristic of cirrhosis is scarring which results in a structurally distorted and dysfunctional liver. Previously, we demonstrated that Col1a1 and Pparg genes are deregulated in CCl 4 -induced cirrhosis but their normal expression levels are recovered upon treatment with IFC-305, an adenosine derivative. We observed that adenosine was able to modulate S-adenosylmethionine-dependent transmethylation reactions, and recently, we found that IFC-305 modulates HDAC3 expression. Here, we investigated whether epigenetic mechanisms, involving DNA methylation processes and histone acetylation, could explain the re-establishment of gene expression mediated by IFC-305 in cirrhosis. Therefore, Wistar rats were CCl 4 treated and a sub-group received IFC-305 to reverse fibrosis. Global changes in DNA methylation, 5-hydroxymethylation, and histone H4 acetylation were observed after treatment with IFC-305. In particular, during cirrhosis, the Pparg gene promoter is depleted of histone H4 acetylation, whereas IFC-305 administration restores normal histone acetylation levels which correlates with an increase of Pparg transcript and protein levels. In contrast, the promoter of Col1a1 gene is hypomethylated during cirrhosis but gains DNA methylation upon treatment with IFC-305 which correlates with a reduction of Col1a1 transcript and protein levels. Our results suggest a model in which cirrhosis results in a general loss of permissive chromatin histone marks which triggers the repression of the Pparg gene and the upregulation of the Col1a1 gene. Treatment with IFC-305 restores epigenetic modifications globally and specifically at the promoters of Pparg and Col1a1 genes. These results reveal one of the mechanisms of action of IFC-305 and suggest a possible therapeutic function in cirrhosis.

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Recovery of the Cell Cycle Inhibition inCCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305

Cited by 15 publications

References 43 publications

Molecular and Cellular Aspects of Cirrhosis and How an Adenosine Derivative Could Revert Fibrosis

Molecular and Cellular Aspects of Cirrhosis and How an Adenosine Derivative Could Revert Fibrosis

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

Epigenetic Effects of an Adenosine Derivative in a Wistar Rat Model of Liver Cirrhosis

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