Role of airway epithelial cells in the development of different asthma phenotypes

Potaczek, Daniel P.; Miethe, Sarah; Schindler, Viktoria; Alhamdan, Fahd; Garn, Holger

doi:10.1016/j.cellsig.2019.109523

Cited by 72 publications

(63 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that hyperacetylation of histone H3 and H3K9 might be involved in gene transcription regulation. Interestingly, histone acetylation was shown to be involved in transcriptional regulation of EMT-related genes and associated pathways [36][37][38], and lactate increases H3K9ac mark, as well as global histone acetylation [17].…”

Section: Discussionmentioning

confidence: 99%

Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation

Miranda‐Gonçalves

Lameirinhas

Macedo-Silva

et al. 2020

Cells

View full text Add to dashboard Cite

Background: Renal cell carcinoma (RCC) displays a glycolytic phenotype (Warburg effect). Increased lactate production, impacting on tumor biology and microenvironment modulation, has been implicated in epigenetic mechanisms' regulation, leading to histone deacetylases inhibition. Thus, in-depth knowledge of lactate's impact on epigenome regulation of highly glycolytic tumors might allow for new therapeutic strategies. Herein, we investigated how extracellular lactate affected sirtuin 1 activity, a class III histone deacetylase (sirtuins, SIRTs) in RCC. Methods: In vitro and in vivo interactions between lactate and SIRT1 in RCC were investigated in normal kidney and RCC cell lines. Finally, SIRT1 and N-cadherin immunoexpression was assessed in human RCC and normal renal tissues. Results: Lactate inhibited SIRT1 expression in normal kidney and RCC cells, increasing global H3 and H3K9 acetylation. Cells exposed to lactate showed increased cell migration and invasion entailing a mesenchymal phenotype. Treatment with a SIRT1 inhibitor, nicotinamide (NAM), paralleled lactate effects, promoting cell aggressiveness. In contrast, alpha-cyano-4-hydroxycinnamate (CHC), a lactate transporter inhibitor, reversed them by blocking lactate transport. In vivo (chick chorioallantoic membrane (CAM) assay), lactate and NAM exposure were associated with increased tumor size and blood vessel recruitment, whereas CHC displayed the opposite effect. Moreover, primary RCC revealed N-cadherin upregulation whereas SIRT1 expression levels were downregulated compared to normal tissues. Conclusions: In RCC, lactate enhanced aggressiveness and modulated normal kidney cell phenotype, in part through downregulation of SIRT1, unveiling tumor metabolism as a promising therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation

Miranda‐Gonçalves

Lameirinhas

Macedo-Silva

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Endotypes differ across the spectrum of asthma, providing a variable response to standard anti-inflammatory therapy with inhaled corticosteroids (ICS) [ 4 , 5 ], which are presently the mainstream of asthma treatment [ 6 , 7 , 8 ]. Furthermore, different regulatory mechanisms, such as release of a variety of cytokines, chemokines and other mediators, may influence airway epithelium responses [ 9 ]. The different endotypes have been investigated in recent years also through highly sophisticated analysis techniques, such as the “-omic sciences”, which have the potential to identify markers useful either in the diagnosis or as a guide for treatment [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids

et al. 2020

View full text Add to dashboard Cite

Background: “breathomics” enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: “breathomics” can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

show abstract

“…Over the last years, it turned out, however, that the airway epithelium in general and the bronchial epithelium as a major part of it in particular represent a much more complex tissue fulfilling a variety of additional functions such as retrograde transport of inhaled particles, establishment of a biochemical barrier system, and initiation and regulation of innate and adaptive immune mechanisms by release of various cytokines and chemokines. By this, it represents an integrative part of the innate immune system, the coordinated activity of which is essential for maintaining the local tissue and even systemic body integrity (5). To exert these diverse functions, the bronchial epithelium is composed of multiple structurally and/or functionally differing cell types, such as ciliated cells (mucociliary transport), goblet cells (mucus secretion), tuft and M cells (luminal signal sampling and antigen presentation), ionocytes (water regulation), and club cells (mucus and surfactant protein production) (6).…”

Section: Airway Epithelium and Asthmamentioning

confidence: 99%

Epigenetic Regulation of Airway Epithelium Immune Functions in Asthma

et al. 2020

Self Cite

View full text Add to dashboard Cite

Asthma is a chronic inflammatory disease of the respiratory tract characterized by recurrent breathing problems resulting from airway obstruction and hyperresponsiveness. Human airway epithelium plays an important role in the initiation and control of the immune responses to different types of environmental factors contributing to asthma pathogenesis. Using pattern recognition receptors airway epithelium senses external stimuli, such as allergens, microbes, or pollutants, and subsequently secretes endogenous danger signaling molecules alarming and activating dendritic cells. Hence, airway epithelial cells not only mediate innate immune responses but also bridge them with adaptive immune responses involving T and B cells that play a crucial role in the pathogenesis of asthma. The effects of environmental factors on the development of asthma are mediated, at least in part, by epigenetic mechanisms. Those comprise classical epigenetics including DNA methylation and histone modifications affecting transcription, as well as microRNAs influencing translation. The common feature of such mechanisms is that they regulate gene expression without affecting the nucleotide sequence of the genomic DNA. Epigenetic mechanisms play a pivotal role in the regulation of different cell populations involved in asthma pathogenesis, with the remarkable example of T cells. Recently, however, there is increasing evidence that epigenetic mechanisms are also crucial for the regulation of airway epithelial cells, especially in the context of epigenetic transfer of environmental effects contributing to asthma pathogenesis. In this review, we summarize the accumulating evidence for this very important aspect of airway epithelial cell pathobiology.

show abstract

Role of airway epithelial cells in the development of different asthma phenotypes

Cited by 72 publications

References 96 publications

Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation

Lactate Increases Renal Cell Carcinoma Aggressiveness through Sirtuin 1-Dependent Epithelial Mesenchymal Transition Axis Regulation

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids

Epigenetic Regulation of Airway Epithelium Immune Functions in Asthma

Contact Info

Product

Resources

About