Fructose-1,6-bisphosphate induces phenotypic reversion of activated hepatic stellate cell

Mesquita, Fernanda Cristina de; Bitencourt, Shanna; Caberlon, Eduardo; Silva, Gabriela V. da; Basso, Bruno Souza; Schmid, Júlia; Ferreira, Gabriela A.; Oliveira, Fernanda dos Santos de; Oliveira, Jarbas Rodrigues de

doi:10.1016/j.ejphar.2013.09.067

Cited by 15 publications

(12 citation statements)

References 50 publications

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“…Three days after FBP exposure, both healthy and fibrotic cells were significantly affected by FBP in vitro , showing signs of going to a quiescent state that is characteristic of normal fibroblasts. In agreement with these results, previous studies showed that FBP treatment in vitro promotes the deactivation of liver fibroblasts [14] even in the presence of free iron that activates fibroblasts to become myofibroblasts [15]. These results mirror some of the in vivo experiments, showing that FBP can have protective effects in a more complex system such as intact tissues.…”

Section: Discussionsupporting

confidence: 86%

“…However, conflicting results were also reported regarding this effect [10–13]. An earlier study found that activated liver myofibroblasts, or hepatic stellate cells, underwent a phenotype reversal associated with quiescence, decreased proliferation, and accumulation of lipid droplets when treated in vitro with FBP, all of which are characteristics of normal healthy fibroblast [14]. This protective effect of FBP was maintained even when these cells were concomitantly exposed to high doses of free iron, that sustains activation of stellate cells [15].…”

Section: Introductionmentioning

confidence: 99%

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Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired fibroblasts degradation followed by stiffness and loss of lung function. Fructose-1,6-bisphosphate (FBP), an intermediate of glycolytic pathway, decreases PF development, but the underlying mechanism is unknown. To address this issue, PF was induced in vivo using a mouse model, and pulmonary fibroblasts were isolated from healthy and fibrotic animals. In PF model mice, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Fibrotic lung fibroblasts (FLF) treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and α-smooth muscle actin, were also downregulated in FBP-treated FLF. Moreover, matrix metalloproteinase (MMP) 1, responsible for ECM degradation, was produced only in fibroblasts obtained from healthy lungs (HLF) and FBP did not alter its expression. On the other hand, tissue inhibitor of metalloproteinase (TIMP)-1, a MMP1 inhibitor, and MMP2, related to fibroblast tissue-invasion, were predominantly produced by FLF and FBP was able to downregulate its expression. These results demonstrate that FBP may prevent bleomycin-induced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and MMP2 expression.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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“…One study demonstrated up-regulation of heat shock proteins early in the resolution phase [114], while another did not [123]. In a study of cultured HSCs, fructose-1,6-bisphosphate mediated PPARγ activation in cultured HSCs to reduce collagen production and increase lipid content; it is unclear whether this response represents the inactivated phenotype seen in animal models [124].…”

Section: Reversion To An Inactivated Phenotypementioning

confidence: 97%

Stellate Cells and Hepatic Fibrosis

Hasegawa

Wallace

Friedman

2015

Stellate Cells in Health and Disease

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“…This lipocyte-like phenotype has the ability to take up and metabolize retinol similar to HSCs (Guma et al 2001; Pinheiro-Margis et al 1992). Therefore, the GRX cell line is a useful tool in the study of lipid-related changes as also occurring during liver fibrosis (Fortuna et al 2001; Guimarães et al 2007) and the action of molecules in the reversion of the activated phenotype (de Mesquita et al 2013; Stefano et al 2011).…”

Section: In Vitro Models Of Liver Fibrosismentioning

confidence: 99%

Experimental models of liver fibrosis

et al. 2015

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Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

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Fructose-1,6-bisphosphate induces phenotypic reversion of activated hepatic stellate cell

Cited by 15 publications

References 50 publications

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Stellate Cells and Hepatic Fibrosis

Experimental models of liver fibrosis

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