Commentary

Abstract

HIGHLIGHTED TOPICSLung Growth and RepairCommentaryGary C. SieckGary C. SieckJournal of Applied Physiology October 2004, Volume 97Published Online:01 Oct 2004https://doi.org/10.1152/japplphysiol.00789.2004MoreSectionsPDF (10 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat In the first featured article, entitled “Hypoxia-responsive growth factors upregulate periostin and osteopontin expression via distinct signaling pathways in the rat pulmonary arterial smooth muscle cells,” Dr. P. Li and colleagues (1) examine expression of the extracellular matrix adhesion molecules, periostin and osteopontin, in pulmonary arteries of hypoxia-adapted rats. These investigators also explored the signaling pathways that regulate expression of periostin and osteopontin in response to hypoxia and the hypoxia-responsive growth factors, fibroblast growth factor-1 (FGF-1) and angiotensin II (ANG II). This study is the first to demonstrate that, as a generalized extracellular matrix response to hypoxic stress, the lungs and pulmonary arteries express elevated levels of periostin and osteopontin. Pulmonary arterial smooth muscle cells from hypertrophic pulmonary arteries show localized expression of hypoxia-induced periostin. Coupled with the observation that levels of periostin and osteopontin increase concurrently in lungs, this finding suggests that periostin is involved in extracellular matrix formation and pulmonary vascular hypertrophy and remodeling in response to chronic hypoxic exposure. In vitro studies of pulmonary arterial smooth muscle cells show that growth factor-induced expression of periostin and osteopontin is differentially regulated, suggesting that these adhesion molecules play different roles in pulmonary vascular remodeling under pathophysiological conditions.In the second featured article, entitled “Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice,” Dr. K. Tang and colleagues (3) examine the role of apoptosis in the development of emphysema. These investigators used intratracheal delivery of an adeno-associated cre recombinase virus to downregulate expression of pulmonary vascular endothelial growth factor (VEGF) in adult mice. These investigators found that partial inactivation of pulmonary VEGF leads to alveolar septal cell apoptosis, air space enlargement, and increased lung compliance. Presumably, normal and efficient apoptotic pathways clear the resulting apoptotic cells. However, the lung ineffectively regenerates damaged alveolar walls, and, despite restoration of normal cellular levels of pulmonary VEGF, increased alveolar size and decreased elastic recoil persist. The results of this study suggest that significant loss of VEGF and pulmonary cells, even for only a brief period, leads to long-lasting, possibly permanent effects. It also highlights the protective capacity of VEGF in maintaining lung structure. How long or how often the lung can withstand exposure to damaging insults before repair mechanisms are overwhelmed remains to be elucidated. Loss of structure itself raises the question of whether it is possible to devise pharmacological strategies to replace alveolar septal structures with lung-targeted angiogenesis.In the third and final featured article, entitled “Regional lung growth following pneumonectomy assessed by computed tomography,” Dr. P. Ravikumar and colleagues (2) assessed mechanical strain in remaining lung tissue after pneumonectomy. These investigators quantified lobar volumes and density gradients in both normal and postpneumonectomy lungs to determine whether the remaining lobes expand uniformly and whether tissue densities are changed uniformly. This study is conceptually straightforward and utilizes standard computed tomography technology; however, it illustrates for the first time a powerful and novel use of in vivo imaging to quantify regional lung distortion and changes in local volume, lung compliance, and soft tissue density. These changes can be followed noninvasively and serially in a wide range of clinical and investigational applications that include measuring the extent and progression of regional heterogeneity in lung disease or injury, assessing local response to treatment or surgical intervention, and determining normal or abnormal patterns of lung growth.REFERENCES1 Li P, Oparil S, Feng W, and Chen YF. Hypoxia-responsive growth factors upregulate periostin and osteopontin expression via distinct pathways in rat pulmonary arterial smooth muscle cells. J Appl Physiol 97: 1550–1558, 2004.Google Scholar2 Ravikumar P, Yilmaz C, Dane DM, Johnson RL, Estrera AS, and Hsia CCW. Regional lung growth following pneumonectomy assessed by computed tomography. J Appl Physiol 97: 1567–1574, 2004.Google Scholar3 Tang K, Rossiter HB, Wagner PD, and Breen EC. Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice. J Appl Physiol 97: 1559–1566, 2004.Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 97Issue 4October 2004Pages 1549-1549 Copyright & PermissionsCopyright © 2004 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00789.2004History Published online 1 October 2004 Published in print 1 October 2004 Metrics