Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins

Mohd, Muzaida Aminah; Norudin, Nur Adelina Ahmad; Muhammad, Tengku Sifzizul Tengku

doi:10.1016/j.mce.2020.110702

Cited by 6 publications

(6 citation statements)

References 50 publications

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“…Furthermore, and consistent with previous reports, IL6 reduced the secretion of the negative acute-phase proteins ALB, TF, TTR, RBP4 ( Fig. 4 B cluster 3) ( 70 , 71 ).…”

Section: Resultssupporting

confidence: 92%

Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems

Knecht

Eberl

Bantscheff

2022

Molecular & Cellular Proteomics

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“…Furthermore, and consistent with previous reports, IL6 reduced the secretion of the negative acute-phase proteins ALB, TF, TTR, RBP4 ( Fig. 4 B cluster 3) ( 70 , 71 ).…”

Section: Resultssupporting

confidence: 92%

Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems

Knecht

Eberl

Bantscheff

2022

Molecular & Cellular Proteomics

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“…Recent studies reported that IL-6 is an important modulator of RBP4 production in the liver. Mohd et al proposed a new mechanism involving peroxisome proliferator-activated receptor α (PPARα) and different CCAAT/enhancer binding protein (C/EBP) isoforms necessary for the regulation of RBP4 gene expression in response to external stimuli, like IL-6, during physiological changes [50]. However, further research is required to understand the mechanisms by which growing tumors enhance RBP4 levels in other tissues and the difference observed between young and aged mice.…”

Section: Discussionmentioning

confidence: 99%

Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

Papiernik

Urbaniak

Kłopotowska

et al. 2020

Cancers

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Retinol-binding protein 4 (RBP4) is proposed as an adipokine that links obesity and cancer. We analyzed the role of RBP4 in metastasis of breast cancer in patients and in mice bearing metastatic 4T1 and nonmetastatic 67NR mammary gland cancer. We compared the metastatic and angiogenic potential of these cells transduced with Rbp4 (4T1/RBP4 and 67NR/RBP4 cell lines). Higher plasma levels of RBP4 were observed in breast cancer patients with metastatic tumors than in healthy donors and patients with nonmetastatic cancer. Increased levels of RBP4 were observed in plasma, tumor tissue, liver, and abdominal fat. Moreover, the blood vessel network was highly impaired in mice bearing 4T1 as compared to 67NR tumors. RBP4 transductants showed further impairment of blood flow and increased metastatic potential. Exogenous RBP4 increased lung settlement by 67NR and 4T1 cells. In vitro studies showed increased invasive and clonogenic potential of cancer cells treated with or overexpressing RBP4. This effect is not dependent on STAT3 phosphorylation. RBP4 enhances the metastatic potential of breast cancer tumors through a direct effect on cancer cells and through increased endothelial dysfunction and impairment of blood vessels within the tumor.Cancers 2020, 12, 623 2 of 21 cancer pulmonary metastasis. These processes precede the onset of a phenotypic switch in the lung endothelium toward a mesenchymal phenotype (EndMT), which is parallel to the appearance of the first pulmonary metastatic colonies [7]. Therefore, therapeutic strategies that aim to normalize endothelial dysfunction can decrease the metastatic potential of this type of breast cancer [8][9][10].Apart from its involvement in cancer development, endothelial dysfunction plays an important role in the development of cardiovascular diseases and atherosclerosis. Moreover, in type 2 diabetes mellitus, endothelial dysfunction and insulin resistance often coexist at the earliest stage of atherosclerosis with elevation of serum retinol-binding protein 4 (RBP4), a specific retinol transporter in the blood [11]. It is documented that RBP4 induces inflammation of endothelial cells in vitro. This action is due to the stimulation of proinflammatory molecules involved in leukocyte recruitment and their adherence to endothelium, and it is independent of retinol and the RBP4 membrane receptor STRA6 [12]. Endothelial inflammation induced by RBP4 is largely mediated by toll-like receptor 4 (TLR4), and in part, through the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways [13]. Moreover, in isolated aorta rings, RBP4 treatment significantly increased NO production, stimulating the PI3K/Akt/eNOS pathway [14].RBP4, classified as adipokine [15], is proposed as the protein linking obesity and cancer [16]. Studies have shown various correlations between RBP4 plasma/tumor tissue levels and the development of certain types of cancer. For instance, Fei et al. reported lower RBP4 serum levels in patients with colon cancer than in healthy individu...

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“…concluded that PPARγ and PPARα mediate RBP4 gene expression and release in brown adipose tissue, and that thermogenesis activation induces RBP4 gene expression in brown fat through a mechanism involving PGC1α signaling ( 21 ). IL-6 regulates RBP4 transcription through PPARα and CCAAT/enhancer binding protein ( 22 ). RBP4 can indirectly regulate RAR or RXR by controlling the transport of vitamin A ( 23 ).…”

Section: Hepatokines and Fxr/rxr Pparα/rxrα Signaling Pathwaysmentioning

confidence: 99%

Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis

Yang

Lu²,

Zhou³

et al. 2022

Front. Endocrinol.

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Fatty liver disease is a spectrum of liver pathologies ranging from simple hepatic steatosis to non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and culminating with the development of cirrhosis or hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is complex and diverse, and there is a lack of effective treatment measures. In this review, we address hepatokines identified in the pathogenesis of NAFLD and NASH, including the signaling of FXR/RXR, PPARα/RXRα, adipogenesis, hepatic stellate cell activation/liver fibrosis, AMPK/NF-κB, and type 2 diabetes. We also highlight the interaction between hepatokines, and cytokines or peptides secreted from muscle (myokines), adipose tissue (adipokines), and hepatic stellate cells (stellakines) in response to certain nutritional and physical activity. Cytokines exert autocrine, paracrine, or endocrine effects on the pathogenesis of NAFLD and NASH. Characterizing signaling pathways and crosstalk amongst muscle, adipose tissue, hepatic stellate cells and other liver cells will enhance our understanding of interorgan communication and potentially serve to accelerate the development of treatments for NAFLD and NASH.

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Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins

Cited by 6 publications

References 50 publications

Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems

Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems

Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis

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