Visfatin induces MUC8 and MUC5B expression via p38 MAPK/ROS/NF-κB in human airway epithelial cells

Youn, Song， Si; Jung, Eun Chae; Bae, Chang Hoon; Choi, Yoon Seok; Kim, Yong Dae

doi:10.1186/1423-0127-21-49

Cited by 28 publications

(13 citation statements)

References 18 publications

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“…It is well known that NAMPT treatment activates various signalling pathways, including PRKA, AKT1, MAPK3/1 and MAPK14, in different cell types (Cheng et al 2011, Brandauer et al 2013, Reverchon et al 2013a, Song et al 2014. We showed that in hen granulosa cells from F1 hierarchical follicles, NAMPT treatment decreased MAPK3/1 phosphorylation after 30 or 60 min of stimulation (Fig.…”

Section: Signalling Pathways Involved In the Nampt Effects In Hen Gramentioning

confidence: 51%

Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells

Diot¹,

Reverchon²,

Ramé³

et al. 2015

Reproduction

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In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine produced by adipose tissue that is found in intracellular and extracellular compartments. The intracellular form of NAMPT is a nicotinamide phosphoribosyltransferase, whereas the extracellular form is considered an adipokine. In humans, NAMPT regulates energy metabolism and reproductive functions, such as ovarian steroidogenesis. To date, no study has investigated the role of NAMPT in hen ovaries. We investigated whether NAMPT is present in hen ovarian follicles and its role in granulosa cells. Using RT-PCR, western blotting and immunocytochemistry, we detected mRNA transcripts and proteins related to NAMPT in theca and granulosa cells from pre-ovulatory follicles. Using RT-PCR, we demonstrated that mRNA NAMPT levels were higher in granulosa cells than they were in theca cells and that during follicle development, theca cell levels decreased, whereas levels remained unchanged in granulosa cells. NAMPT protein quantities were significantly higher in theca cells than they were in granulosa cells, but they were unchanged during follicular development. Plasma NAMPT levels, as determined by ELISA and immunoblotting, were significantly lower in adult hens than they were in juveniles. In vitro, treatment with human recombinant NAMPT (100 ng/ml, 48 h) halved basal and IGF1-induced progesterone secretion, and this was associated with a reduction in STAR and HSD3B protein levels and MAPK3/1 phosphorylation levels in granulosa cells. These effects were abolished by the addition of FK866, a specific inhibitor of NAMPT enzymatic activity. Moreover, NAMPT had no effect on granulosa cell proliferation. In conclusion, NAMPT is present in hen ovarian cells and inhibits progesterone production in granulosa cells.

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Section: Signalling Pathways Involved In the Nampt Effects In Hen Gramentioning

confidence: 51%

Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells

Diot¹,

Reverchon²,

Ramé³

et al. 2015

Reproduction

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“…Not surprisingly, many immune stimulants were found to increase MUC5B expression including visfatin (proinflammatory adipocytokine) [309], lipopolysaccharide [310], IL-13 [311], adenosine monophosphate-activated protein kinase [312], monocyte chemotactic protein 1 [313], IL-8 [314], prostaglandin [315], and staphylococcus enterotoxin A [316].…”

Section: Introductionmentioning

confidence: 99%

“…The components of this pathway that have been specifically implicated in MUC5B regulation include p38 MAPK, ERK, NF-κB, MMP-9, ROS, RSK1, CREB, IL-1β, and IL-17A [157,305,309,312,[315][316][317][319][320][321]. This pathway is undoubtedly contributing to the regulation/dysregulation of MUC5B, likely acting through a proximal promoter [322].…”

Section: Introductionmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

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Idiopathic pulmonary fibrosis (IPF) is the most common and the most aggressive fibrosing interstitial lung disease (ILD). Despite recent promising clinical trials, IPF remains incurable and largely untreatable. Genetic studies have identified several risk loci for both sporadic and familial forms of IPF. A single variant upstream of MUC5B is predicted to account for more than 30% of all IPF risk. This variant, rs35705950, is associated with expression of MUC5B in healthy lung tissue. However, the mechanism underlying the relationship between rs35705950 and MUC5B expression remains unclear.The first goal of my thesis research was to determine whether rs35705950 is also a risk factor for other forms of ILD. Genomic DNA from individuals with IPF, HP, COPD, iNSIP, and RB-ILD was obtained and genotyped for the common MUC5B promoter variant. In these populations the risk allele was associated with IPF and iNSIP which suggested a potential shared disease mechanism. Additionally, I showed that in the IPF and control populations rs35705950 is associated with lung MUC5B expression.The second goal of my thesis research was to investigate MUC5B promoter DNA methylation which has previously been shown to play a role in MUC5B expression.Methylation analysis of the 4KB region upstream of MUC5B identified two differentially methylated regions (DMRs) associated with IPF, one DMR associated with MUC5B iv expression, and one DMR associated with rs35705950. The IPF, MUC5B expression, and rs35705950 associated DMRs are all differentially methylated at a cluster of 11 CpG motifs. overlapping DMR, including the motif disrupted by rs35705950. These findings suggest that DNA methylation may play a role in MUC5B gene regulation and IPF risk.Next, I used cross species analysis to identify highly conserved domains within the overlapping DMR. Evolutionary conservation indicated selective pressures to maintain sequences overtime and suggests biological importance. The overlapping DMR contains a highly conserved binding motif for FOXA2, a transcription factor. Further analysis using ChIP-qPCR, reporter constructs, and siRNA, established a role for FOXA2 in regulation of MUC5B expression in lung tissue. Additionally, siRNA knock down identified 3 other transcription factors which are associated with MUC5B expression; STAT3, HOXA9 and ZBTB7A. These transcriptional regulators provide insight into possible therapeutic intervention for MUC5B dysregulation and IPF.The form and content of this abstract are approved. I recommend its publication.

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“…The NF-κB agonist LPS (10 μg/mL) and inhibitor PDTC (10 μM) were used to activate or suppress NF-κB in ATO-treated cells. Previous studies showed that LPS and PDTC at these two dosages can sufficiently activate or inhibit NF-κB without affecting cell growth in many cell lines, including HepG2 cells (Jeong et al, 2014;Song et al, 2014). The result demonstrated that ATO dosedependently decreased cell viability (Fig.…”

Section: Parp-1 Inhibitor 4an Sensitized Ato In Hepg2 Cells and Thismentioning

confidence: 75%

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

et al. 2015

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-The therapeutic efficacy of arsenic trioxide (ATO) for treatments of solid tumors is restricted by its drug resistance and chemotoxicity. In this study, we investigated ATO sensitization and detoxification effect of the Poly (ADP ribose) polymerase-1 (PARP-1) inhibitor 4-Amino-1,8-naphthalimide (4AN) in the hepatocellular carcinoma cell line HepG2. We firstly reported that ATO treatment induced the activation of Nuclear factor of κB (NF-κB) and its downstream anti-apoptosis and pro-inflammatory effectors in a PARP-1-dependent manner and thus conferred HepG2 cells with ATO resistance and toxicity. 4AN significantly suppressed the ATO-induced NF-κB activation, which promotes the apoptotic response and alleviates the inflammatory reaction induced by ATO, resulting in sensitization and detoxification against ATO. We also demonstrated that the ATO-induced activation of PARP-1 and NF-κB was closely associated with the oxidative DNA damage mediated by the generated reactive oxygen species (ROS). Furthermore, the attenuation of ATO-induced ROS and the resulting oxidative DNA damage by N-acetyl-L-cysteine (NAC), a potent antioxidant, significantly reduced the activation of PARP-1 and NF-κB in ATO-treated cells. Our study provides novel insights into the mechanism of the PARP-1-mediated NF-κB signaling pathway in ATO resistance and toxicity in anticancer treatments. This study also highlights the application potential of PARP-1 inhibitors in ATO-based anti-cancer treatments and in prevention of NF-κB-mediated therapeutic resistance and toxicity.

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Visfatin induces MUC8 and MUC5B expression via p38 MAPK/ROS/NF-κB in human airway epithelial cells

Cited by 28 publications

References 18 publications

Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells

Expression and effect of NAMPT (visfatin) on progesterone secretion in hen granulosa cells

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

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