HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia: An immunohistochemical/molecular exploratory study

Quelhas, Patrícia; Breton, Michele Claire; Oliveira, Rui Caetano; Cipriano, Maria Augusta; Teixeira, Paulo Ivo Cortez; Cerski, Carlos Thadeu Schmidt; Shivakumar, Pranavkumar; Vieira, Sandra Maria Gonçalves; Kieling, Carlos Oscar; Verde, Ignácio; Santos, Jorge Luiz dos

doi:10.1016/j.jpedsurg.2022.08.020

Cited by 6 publications

(3 citation statements)

References 59 publications

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“…Our previous studies have demonstrated that FTA may exert hepatoprotective effects by regulating the apoptosis pathway mediated by the PI3K-Akt signaling pathway [63]. Chronic liver injury caused by cholestasis may lead to anoxic areas in the liver that may induce HIF-1α activation, which further regulates a variety of fibrotic mediators, and stimulates the overproduction of collagen and liver fibrosis [64][65][66]. In the cholestasis of pregnancy, prolactin and its receptors are involved in water-salt metabolism and in turn, affect liver bile excretion [67][68][69].…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

Dai

et al. 2023

Nutrients

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Forsythia fruit, edible fruit of Forsythia suspensa (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and p-NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.

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Section: Discussionmentioning

confidence: 99%

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

Dai

et al. 2023

Nutrients

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“…The presence of HIF-1αpositive in ammatory cellular in ltrates in the porta hepatitis suggests the existence of an integrated network of processes involving hypoxia, in ammation, brosis, and biliary obstruction. Quelhas et al hypothesized the molecular biological mechanism of pathogenesis of BA that an injurious agent affecting the vascular endothelium of peribiliary vascular plexus would lead to endothelial dysfunction and secondary ischemic cholangiopathy (4,21). Activation of the HIF-1alpha pathway may be associated with the pathogenesis of BA.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of familial clustering of BA cases suggests a possible role of inherited factors. Some studies have identi ed genetic variations associated with BA, including genes involved in biliary development and immune regulation (4).…”

Section: Introductionmentioning

confidence: 99%

HIF-1α is an important target for future research on the etiology and treatment of biliary atresia

Ruifeng,

Duan

2023

Preprint

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Purpose of the study: In this study, our objective was to discover and immunologically profile clusters of molecules associated with copper-induced cell death in biliary atresia (BA) by employing a bioinformatics approach. We conducted an analysis of the GSE46960 dataset, sourced from the Gene Expression Omnibus (GEO), to gain insights into the involvement of copper-related molecular clusters in the development of BA. Study design: We conducted our study using liver samples collected from 64 children diagnosed with biliary atresia and compared them with 14 age-matched children suffering from other cholestatic diseases. Our investigation revolved around the identification of molecular clusters based on cuproptosis-related genes, while also examining the associated immune cell infiltration. To pinpoint genes specific to each cluster, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm. Results: We identified dysregulated cuproptosis-related genes and observed activated immune responses in the comparison between biliary atresia and non-biliary atresia control groups. Within biliary atresia, we categorized two distinct cuproptosis-related molecular clusters. Our analysis of immune infiltration indicated notable differences in immune profiles between these two clusters, with Cluster2 displaying relatively higher levels of immune infiltration. Functional analysis further revealed that the cluster-specific Differentially Expressed Genes (DEGs) in Cluster2 were closely associated with a variety of immune responses. Conclusions: Our study provides a comprehensive depiction of the intricate relationship between copper-induced cell death and biliary atresia. Previous research has suggested a potential link between the activation of the HIF-1alpha pathway and the development of biliary atresia, and the findings presented in this paper lend support to this hypothesis.

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Inhibition of Notch3/Hey1 ameliorates peribiliary hypoxia by preventing hypertrophic hepatic arteriopathy in biliary atresia progression

Chang,

Chi,

Zhang

et al. 2024

Histochem Cell Biol

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HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia: An immunohistochemical/molecular exploratory study

Cited by 6 publications

References 59 publications

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

HIF-1α is an important target for future research on the etiology and treatment of biliary atresia

Inhibition of Notch3/Hey1 ameliorates peribiliary hypoxia by preventing hypertrophic hepatic arteriopathy in biliary atresia progression

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