cAMP and Epac in the regulation of tissue fibrosis
Year: 2012
Type: review
Abstract: Fibrosis, the result of excess deposition of extracellular matrix (ECM), in particular collagen, leads to scarring and loss of function in tissues that include the heart, lung, kidney and liver. The second messenger cAMP can inhibit the formation and extent of ECM during this late phase of inflammation, but the mechanisms for these actions of cAMP and of agents that elevate tissue cAMP levels are not well understood. In this article, we review the fibrotic process and focus on two recently recognized aspects of actions of cAMP and its effector Epac (Exchange protein activated by cAMP): (a) blunting of epithelial-mesenchymal transformation (EMT) and (b) down-regulation of Epac expression by profibrotic agents (e.g. TGF-β, angiotensin II), which may promote tissue fibrosis by decreasing Epac-mediated antifibrotic actions. Pharmacological approaches that raise cAMP or blunt the decrease in Epac expression by profibrotic agents may thus be strategies to block or perhaps reverse tissue fibrosis. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.
Source: British Journal of Pharmacology
Authors: Paul A Insel, Fiona Murray, Utako Yokoyama, Silvia Romano, Hongruo Yun, Loren Brown, Aaron Snead, David Lu, Nakon Aroonsakool
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Phosphodiesterase-1 in Pulmonary Hypertension: Expression, Regulation, and Target, G2591686152, Three-dimensional multilayers of smooth muscle cells as a new experimental model for vascular biology, Graduate Training in Cellular and Molecular Pharmacology, The cardiac fibroblast-targeted novel strategy for diastolic heart failure, G713150642, Training in Cardiovascular Physiology and Pharmacology
OpenAlex ID: W1595102068