Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.
Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Br J Pharmacol. 2019 Jul;176(14):2402-2415. doi: 10.1111/bph.14605. Epub 2019 Mar 18.
Over the past decades, research has defined cAMP as one of the central cellular nodes in sensing and integrating multiple pathways and as a pivotal role player in lung pathophysiology. Obstructive lung disorders, such as chronic obstructive pulmonary disease (COPD), are characterized by a persistent and progressive airflow limitation and by oxidative stress from endogenous and exogenous insults. The extent of airflow obstruction depends on the relative deposition of different constituents of the extracellular matrix, a process related to epithelial-to-mesenchymal transition, and which subsequently results in airway fibrosis. Oxidative stress from endogenous and also from exogenous sources causes a profound worsening of COPD. Here we describe how cAMP scaffolds and their different signalosomes in different subcellular compartments may contribute to COPD. Future research will require translational studies to alleviate disease symptoms by pharmacologically targeting the cAMP scaffolds. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
在过去的几十年中，研究已经将 cAMP 定义为感知和整合多种途径的细胞内核心节点之一，也是肺病理生理学中的关键角色扮演者。阻塞性肺疾病，如慢性阻塞性肺疾病（COPD），其特征是持续和进行性的气流受限，以及内源性和外源性损伤引起的氧化应激。气流阻塞的程度取决于细胞外基质的不同成分的相对沉积，这一过程与上皮-间充质转化有关，随后导致气道纤维化。内源性和外源性来源的氧化应激会导致 COPD 严重恶化。在这里，我们描述了 cAMP 支架及其在不同亚细胞隔室中的不同信号体如何有助于 COPD。未来的研究需要通过药理学靶向 cAMP 支架来减轻疾病症状的转化研究。相关文章：本文是关于肾上腺素能受体-旧角色的新作用的专题部分的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
