BET proteins are associated with the induction of small airway fibrosis in COPD
نویسندگان
چکیده
Rationale In COPD, small airway fibrosis occurs due to increased extracellular matrix (ECM) deposition in and around the smooth muscle (ASM) layer. Studies of immune cells peripheral lung tissue have shown that epigenetic changes occur COPD but it is unknown whether mesenchymal are reprogrammed. Objectives Determine if ASM a unique response profibrotic cytokine transforming growth factor ?1 (TGF-?1). Methods Primary human from non-COPD smoking patients were stimulated with TGF-?1. Gene array analysis performed identify differences ECM expression. Airway accumulation collagen 15?1 tenascin-C proteins was assessed. Aforementioned TGF-?1 ± inhibitors qPCR quantification COL15A1 TNC . Global histone acetyltransferase (HAT) deacetylase (HDAC) activity chromatin immunoprecipitation (ChIP)-qPCR for H3 H4 acetylation at promoters carried out. Effects bromoterminal extraterminal domain (BET) inhibitor JQ1(+) on expression target genes Measurements main results show significantly higher vitro same trend levels tenascin-c deposited airways vivo. Epigenetic screening indicated differential HDAC inhibition. ChIP-qPCR revealed only. found pretreatment abrogated induced Conclusions BET protein binding acetylated histones important maintenance cell progeny.
منابع مشابه
T-bet polymorphisms are associated with asthma and airway hyperresponsiveness.
RATIONALE T-bet (TBX21 or T-box 21) is a critical regulator of T-helper 1 lineage commitment and IFN-gamma production. Knockout mice lacking T-bet develop airway hyperresponsiveness (AHR) to methacholine, peribronchial eosinophilic and lymphocytic inflammation, and increased type III collagen deposition below the bronchial epithelium basement membrane, reminiscent of both acute and chronic asth...
متن کاملThe Relationship between the Severity of Airway Obstruction and COPD Diagnostic Questionnaire Score in COPD Patients
Background & objectives: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and systemic inflammation which is also associated with pulmonary and extra-pulmonary complications. COPD Diagnostic Questionnaire (CDQ) is a valid questionnaire that is used to identify patients with COPD. The purpose of this study was to determine the relationship between ...
متن کاملGenetic variants in ADAM33 are associated with airway inflammation and lung function in COPD
BACKGROUND Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile. Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung functio...
متن کاملthe study of aaag repeat polymorphism in promoter of errg gene and its association with the risk of breast cancer in isfahan region
چکیده: سرطان پستان دومین عامل مرگ مرتبط با سرطان در خانم ها است. از آنجا که سرطان پستان یک تومور وابسته به هورمون است، می تواند توسط وضعیت هورمون های استروئیدی شامل استروژن و پروژسترون تنظیم شود. استروژن نقش مهمی در توسعه و پیشرفت سرطان پستان ایفا می کند و تاثیر خود را روی بیان ژن های هدف از طریق گیرنده های استروژن اعمال می کند. اما گروه دیگری از گیرنده های هسته ای به نام گیرنده های مرتبط به ا...
15 صفحه اولذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Thorax
سال: 2021
ISSN: ['1468-3296', '0040-6376']
DOI: https://doi.org/10.1136/thoraxjnl-2020-215092