Defective Histone Acetylation Is Responsible for the Diminished Expression of Cyclooxygenase-2 in Idiopathic Pulmonary Fibrosis.

Coward, William R.; Watts, Keira; Feghali‐Bostwick, Carol; Knox, AJ; Pang, Linhua

doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3977

Cited by 50 publications

(89 citation statements)

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“…In accordance with these data, there is also evidence for altered DNA methylation in IPF lungs: epigenome analysis revealed globally altered methylation patterns of hundreds of CpG islands, but also of specific promoters of genes implicated in lung fibrosis, which correlated with altered expression of the respective genes [217][218][219][220][221]. In addition to DNA methylation, epigenetic histone modifications, in particular those mediated by HDACs, may contribute to lung fibrosis, as they were shown to regulate expression of single target genes of pulmonary fibrosis [220,222].…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases. @ERSpublications Hallmarks of ageing are selecting factors for the pathogenesis of COPD, lung cancer and IPF

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Section: Epigenetic Alterationsmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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“…Methods were adapted from those published by Knox and colleagues (16,20,25). Details are provided in the online supplement.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

“…Epigenetic regulation of COX-2 expression is an emerging area of interest, and controller mechanisms include microRNAs (e.g., microRNA [miR]-155) and histone posttranslation modifications (e.g., acetylation) (16)(17)(18)(19). Indeed, reduced histone acetylation and miR-146a expression have been linked to alterations in COX-2 expression in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, respectively (17,20). These regulatory mechanisms have been demonstrated to be altered in asthmatic hASMCs (21,22) but not in the context of COX-2 expression.…”

mentioning

confidence: 99%

Cyclooxygenase-2 and MicroRNA-155 Expression Are Elevated in Asthmatic Airway Smooth Muscle Cells

Comer

Camoretti-Mercado

Kogut³

et al. 2015

Am J Respir Cell Mol Biol

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Cyclooxygenase-2 (COX-2) expression and PGE 2 secretion from human airway smooth muscle cells (hASMCs) may contribute to b 2 -adrenoceptor hyporesponsiveness, a clinical feature observed in some patients with asthma. hASMCs from patients with asthma exhibit elevated expression of cytokine-responsive genes, and in some instances this is attributable to an altered histone code and/or microRNA expression. We hypothesized that COX-2 expression and PGE 2 secretion might be elevated in asthmatic hASMCs in response to proinflammatory signals in part due to altered histone acetylation and/or microRNA expression. hASMCs obtained from nonasthmatic and asthmatic human subjects were treated with cytomix (IL-1b, TNF-a, and IFN-g). A greater elevation of COX-2 mRNA, COX-2 protein, and PGE 2 secretion was observed in the asthmatic cells. We investigated histone H3/H4-acetylation, transcription factor binding, mRNA stability, p38 mitogen-activated protein kinase signaling, and microRNA (miR)-155 expression as potential mechanisms responsible for the differential elevation of COX-2 expression. We found that histone H3/H4-acetylation and transcription factor binding to the COX-2 promoter were similar in both groups, and histone H3/H4-acetylation did not increase after cytomix treatment. Cytomix treatment elevated NF-kB and RNA polymerase II binding to similar levels in both groups. COX-2 mRNA stability was increased in asthmatic cells. MiR-155 expression was higher in cytomix-treated asthmatic cells, and we show it enhances COX-2 expression and PGE 2 secretion in asthmatic and nonasthmatic hASMCs. Thus, miR-155 expression positively correlates with COX-2 expression in the asthmatic hASMCs and may contribute to the elevated expression observed in these cells. These findings may explain, at least in part, b 2 -adrenoceptor hyporesponsiveness in patients with asthma.

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“…The PGE 2 is produced from endogenous arachidonic acid via the cyclooxygenase (COX) pathway. In this context, it was demonstrated that COX-2 gene transcription in IPF fibroblasts is defective due to deficient histone H3 and H4 acetylation as a result of decreased recruitment of histone acetyltransferase and increased recruitment of the several transcriptional corepressor complexes to the COX-2 promoter 33 . These findings indicate that defective histone acetylation contributes to the decrease of COX-2 gene transcription in IPF.…”

Section: Histone Modifications and Chromatin Remodelingmentioning

confidence: 99%