Every three months, the Editor and Deputy Editors select five articles for inclusion in the FEATURED ARTICLE section of the AJP-Lung web page. (http://ajplung.physiology.org/) These articles are likely to have a significant impact on their fields and they are the best demonstration of the excellence of AJP-Lung. They can be downloaded in their entirety even if a reader does not have a subscription to the journal. A brief summary of one of these articles is provided by Dr. Rory Morty, Deputy Editor, of AJP-Lung.
Sadis Matalon, Editor in Chief.
The extracellular matrix (ECM) has long been accredited with pathophysiological roles in the lung. A large volume of important work has addressed the ECM in lung disease, largely by examining the abundance or paucity of key ECM molecules, notably collagen and elastin, in the lungs of experimental animals or clinical subjects with lung disease. Little attention has been paid to how perturbations to ECM structure actually impact the physiological function of the ECM, particularly related to how the ECM structure may drive phenotypic changes in the behavior of lung cells that rest, or are in contact with, the underlying ECM. This is particularly important in tissues where disease processes results in major changes in the composition or distribution of the ECM. In a recent issue of the Journal, Shkumatov and colleagues report on how changes in the mechanical stiffness of a model matrix can influence the behavior of airway smooth muscle cells (ASMC). In their study, the investigators cultured ASMC on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli. The remarkable observations were (i) that “softer” gels caused increased secretion of pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) by ASMC while in contrast; (ii) “harder” gels stimulated ASMC proliferation and reduced both VEGF secretion and histamine-induced calcium responses. These responses were correlated with the expression of components of the integrin system, namely integrin-beta1 and the integrin-linked kinase. Thus, the authors conclusively demonstrate that ASMC are very responsive to the mechanical stiffness of collagen-conjugated hydrogels, which are useful and elegant models of cell adhesion matrices that can be manipulated to alter the elastic modulus. These studies contribute enormously to an emerging body of work that has started to address how the properties (as opposed to the abundance) of the ECM may drive pathological (and indeed, normal physiological) processes. The authors are to be commended on a most interesting study, which will undoubtedly form the basis of further exciting studies that we hope to see published in the pages of the Journal in the future.
Commentary by Dr. Rory Morty, Deputy Editor AJP-Lung