Fructose-1,6-Bisphosphate Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice and Inhibits the Proliferation of Lung Fibroblasts

Jost, Renan Trevisan; Dias, Henrique Bregolin; Krause, Gabriele Catyana; Souza, Rodrigo Matos de; Souza, Tássia Rezende de; Nuñez, Nailê Karine; Santos, Fernanda Greinert dos; Haute, Gabriela Viegas; Melo, Denizar Alberto da Silva; Pitrez, Paulo Márcio; Silva, Vinícius Duval da; Donadio, Márcio Vinı́cius Fagundes; Oliveira, Jarbas Rodrigues de

doi:10.1007/s10753-018-0842-3

Cited by 7 publications

(10 citation statements)

References 45 publications

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“…FBP is a metabolite from glycolysis produced by phosphofructokinase-1, that has many protective properties [13, 16]. In this study, the effects of FBP were evaluated in an experimental model of BLM-induced PF and in in vitro studies using lung fibroblasts derived from healthy and fibrotic mice.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study [16] showed that a single dose of FBP given at the time of BLM administration can prevent PF, with improvement of lung function. In the current study, mice were administered FBP once a day for 14 consecutive days.…”

Section: Discussionmentioning

confidence: 99%

“…In the earlier studies, a human cell lineage of lung fetal fibroblasts were used [16]. Fetal and adult fibroblasts behave in different ways.…”

Section: Discussionmentioning

confidence: 99%

“…Male mice (eight week old, C57Bl/6N, 25-30g) maintained in a 12h light-dark cycle with water and chow ad libitum , were divided into four groups; 1) Bleomycin (BLM) group: received intratracheally (IT) 1.2U/kg BLM (Sigma-Aldrich) on day 0 [17], 2) control group: received IT an equal volume of saline on day 0, 3) BLM + FBP group; BLM IT on day 0 and thereafter daily intraperitoneal injection (ip) of 500 mg/kg FBP [16, 18] for 14 days, and 4) FBP group: saline IT on day 0 and thereafter daily ip of FBP. Weight and mortality were monitored daily for 14 days.…”

Section: Methodsmentioning

confidence: 99%

“…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]. A previous study on lung fibrosis showed that FBP can prevent bleomycin-induced fibrosis development in mice [16], however, the molecular basis of this effect remains unknown. The aim of this study was to determine how FBP prevents and/or regulates the fibrotic process using an animal model of PF induced by bleomycin in vivo and primary fibroblasts isolated from healthy and fibrotic lungs of mice in vitro .…”

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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In the earlier studies, a human cell lineage of lung fetal fibroblasts were used [16]. Fetal and adult fibroblasts behave in different ways.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

Costa

Nassr

Diz

et al. 2020

J of Applied Toxicology

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Fructose‐1,6‐bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non‐cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro‐apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP‐treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53‐dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

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Dehydrozingerone alleviates pulmonary fibrosis via inhibition of inflammation and epithelial-mesenchymal transition by regulating the Wnt/β-catenin pathway

Shaikh

Kuncha

Andugulapati

et al. 2023

European Journal of Pharmacology

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Fructose-1,6-Bisphosphate Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice and Inhibits the Proliferation of Lung Fibroblasts

Cited by 7 publications

References 45 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

Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

Dehydrozingerone alleviates pulmonary fibrosis via inhibition of inflammation and epithelial-mesenchymal transition by regulating the Wnt/β-catenin pathway

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