The importance of epigenetics in the development of chronic obstructive pulmonary disease

Abstract

It is generally accepted that genetic predisposition plays a role in COPD development in susceptible individuals. Therefore, many candidate genes that could be linked to the development of disease have been examined in COPD. However, inconsistent results in different study populations often limit this approach, suggesting that not only genetics, but also other factors, may be contributed to the susceptibility to COPD. Epigenetic mechanisms can affect the transcriptional activity of specific genes, at different points in time, and in different organs. Moreover, these mechanisms can have an effect on people's health. Recently, there is emerging evidence supporting a role of epigenetics for the regulation of inflammatory genes in diseases such as asthma and COPD. Moreover, recent studies suggest that the currently used treatments including corticosteroids may work through epigenetic mechanisms. Epigenetic regulation can be reprogrammed, potentially affecting the risk, aetiology and treatment of various disease states. The epigenetically influenced phenotype could be reversed with demethylating or deacetylating agents, consistent with epigenetic plasticity. The postnatal reversibility of these methylation or acetylation events may therefore provide good opportunities for intervention.The recognition of the role of genetic and epigenetic mechanisms in the development of COPD may identify novel targets that hatch new therapies for patients with COPD.

Methylation of the Human Pendrin Promoter

“…What is becoming even more evident is the importance of epigenetic regulation in the future and retrospective lead search and optimization of therapies for these diseases [45][46][47][48][49][50]. Further functional studies are needed to determine if and how methylation within the pendrin promoter alters SLC26A4 gene expression, and in what context this type of epigenetic regulation has in pendrin-associated disease.…”

Involvement of B-cell CLL/lymphoma 2 promoter methylation in cigarette smoke extract-induced emphysema

“…The CSE group mice were injected intraperitoneally with CSE at day 0, 11, 22 of the study, and injected with 0.3 mL PBS at day 15, 17, 19 of study. While the control group mice were administrated with 0.3 mL PBS in the same way at day 0, 11,15,17,19,22. The CSE þ AZA group was injected with intraperitoneally with 0.3 mL CSE at day 0, 11, 22, and AZA at day 15,17,19.…”

“…17,18 Promoter methylation leads the condensation of chromatin into a compact state, which is inaccessible by transcription factors, causing a down-regulation of exon expression. 19 Recent studies also demonstrated the involvement of epigenetics in COPD, 19,20 and our previous study showed demethylation might protect models from emphysema. 21 Thus, the methylation-related apoptosis might play a role in emphysema pathogenesis.…”

Epigenetic and current treatment approaches in chronic obstructive pulmonary disease

“…(34). SIRT1'in fosforilasyonunu inhibe eden yeni farmakolojik tedaviler KOAH'lı hastalarda inflamasyonu iyileştirebilir ancak steroid direncini düzeltmedeki etkileri henüz bilinmemektedir (35). KOAH'ta oksidatif stresle artan ve IL-1 tarafından uyarılan IL-6, IL-8 (KC) ekspresyonu bromodomain ve ekstraterminal proteinlerce (BET) baskılanarak antiinflamatuvar tedavi sağlanabileceği söylenmiştir (36).…”