Fatty acid binding protein-4 promotes alcohol-dependent hepatosteatosis and hepatocellular carcinoma progression

Attal, Neha; Sullivan, Mariel; Girardi, Cara; Thompson, Kyle J.; McKillop, Iain H.

doi:10.1016/j.tranon.2020.100975

Cited by 16 publications

(23 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, Fabp1 is increased in simple steatosis (128%), when compared to obese normal patients; however, it is under-expressed in nonalcoholic steatohepatitis ( 36 ), suggesting that FABP1 may function in a context-dependent manner. Fabp4 mRNA expression has been shown highly induced by chronic alcohol exposure ( 37 ), consistent with our observations ( Fig. 3 D ).…”

Section: Discussionsupporting

confidence: 93%

MicroRNA-200c coordinates HNF1 homeobox B and apolipoprotein O functions to modulate lipid homeostasis in alcoholic fatty liver disease

Mostofa

Tran

Gilling

et al. 2022

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

MicroRNA-200c coordinates HNF1 homeobox B and apolipoprotein O functions to modulate lipid homeostasis in alcoholic fatty liver disease

Mostofa

Tran

Gilling

et al. 2022

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…A flow chart of the overall research is shown in Figure S1. 30 genes were chosen based on their roles in previous studies (27)(28)(29)(30)(31)(32)(33). The majority of FA metabolism-related genes were identified as DEGs (p < 0.05) using Heatmap analysis (Figure 1A).…”

Section: Identification Of Fa Metabolism-related Degs Between Normal ...mentioning

confidence: 99%

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Zhu

Zhu²,

Chen³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundLiver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients’ prognosis prediction.MethodsWe collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1.ResultsAccording to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA.ConclusionOur study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.

show abstract

“…Interestingly, our in vitro results showed that FABP4 expression was increased in a time- and dose-dependent manner in CSE-treated 16HBE cells, a human bronchial epithelial cell line. FABP4 mainly plays a role in regulating metabolism and inflammation pathways [ 17 , 26 – 28 ]. Chlamydia pneumoniae in mice infects and proliferates fat cells by inducing hormone-sensitive lipase-mediated lipolysis [ 7 ], and strongly induces fat cells to secrete FABP4 by stimulating endoplasmic reticulum stress and unfolded protein response [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke extract-mediated FABP4 upregulation suppresses viability and induces apoptosis, inflammation and oxidative stress of bronchial epithelial cells by activating p38 MAPK/MK2 signaling pathway

Zhang

Zhang²,

Zhu

2022

J Inflamm

View full text Add to dashboard Cite

Background Long-term inhalation of cigarette smoke is considered to be one of the main causes of bronchial epithelioid cell damage, but its underlying mechanism has to be further clarified. Methods Gene expression at mRNA level and protein levels were detected by qRT-PCR and western blot analysis respectively. CCK-8, TUNEL assays, ELISA, western blot analysis and commercial kits were utilized to test cell viability, apoptosis inflammatory response and oxidative stress. The correlation between fatty acid binding protein 4 (FABP4) and the p38 mitogen-activated protein kinase (MAPK)/MAPK activated kinase 2 (MK2) signaling pathway was verified by western blot analysis and rescue assays. Results Cigarette smoke extract (CSE) exposure decreased viability, induced apoptosis and inflammatory response in 16HBE cells. Moreover, the expression of FABP4 in CSE-treated 16HBE cells was up-regulated in a time and dose-dependent manner. Ablation of FABP4 in 16HBE cells significantly protected against CSE-mediated cell viability decline and apoptosis. Further, FABP4 knockdown suppressed inflammatory response by down-regulating the elevated levels of cellular inflammatory factors including TNF-α, IL-1β, IL-6, Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) in CSE-treated 16HBE cells. The oxidative stress induced by CSE in 16HBE cells was also inhibited by FABP4 silence as evidence by reduced ROS and MDA level but increased SOD activity caused by FABP4 silence. Finally, all the above effects of FABP4 silence on CSE-treated 16HBE cells were reversed by asiatic acid, an agonist of p38 mitogen-activated protein kinase (MAPK). Conclusions The up-regulation of FABP4 expression mediated by CSE exerted pro-inflammatory, pro-oxidative stress and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK/MK2 signaling pathway. Our findings help to further understand the underlying mechanism of cigarette smoke-induced bronchial inflammation.

show abstract

Fatty acid binding protein-4 promotes alcohol-dependent hepatosteatosis and hepatocellular carcinoma progression

Cited by 16 publications

References 32 publications

MicroRNA-200c coordinates HNF1 homeobox B and apolipoprotein O functions to modulate lipid homeostasis in alcoholic fatty liver disease

MicroRNA-200c coordinates HNF1 homeobox B and apolipoprotein O functions to modulate lipid homeostasis in alcoholic fatty liver disease

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Cigarette smoke extract-mediated FABP4 upregulation suppresses viability and induces apoptosis, inflammation and oxidative stress of bronchial epithelial cells by activating p38 MAPK/MK2 signaling pathway

Contact Info

Product

Resources

About