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EDITORIAL

HIGHLIGHTED TOPIC

Lung growth and repair

In the October issue, in a mini-review entitled "Apoptosis in lung injury and remodeling," Dr. X. Li and colleagues discuss the regulation of apoptosis in lung injury and remodeling with regard to the potential roles of apoptosis in disease pathogenesis. Although these investigators focus their mini-review primarily on the role of apoptosis in such diseases as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis, the data and theories summarized are likely applicable to other forms of lung disease as well.

In a mini-review entitled "Alveolus formation: what have we learned from genetic studies?," Drs. C. Yan and H. Don discuss the use of animal models for investigating the molecular bases of alveolar formation and lung disease. Alveolar formation in the lung can be affected by multiple factors, and mouse gene knock-out and transgenic systems are powerful tools for evaluating the functions of these multifactors in vivo. Recent studies using such systems have demonstrated that surfactant lipids, surfactant proteins, nuclear receptors, and transcription factors play critical roles in lung physiology and pathology.

In the November issue, in a mini-review entitled "Signals and mechanisms of compensatory lung growth," Dr. C. Hsia discusses the mechanistic basis of lung regrowth. Loss of lung units alters mechanical interactions among remaining lung units and between the lung and thorax, inducing adaptations such as recruitment of physiological reserves, remodeling of existing tissue, and regenerative acinar growth when strain exceeds critical threshold. Compensatory growth intensifies the disparity between highly plastic acini and less plastic conducting airways and blood vessels. Such compensatory growth leads to persistent airflow and hemodynamic dysfunction despite vigorous alveolar regeneration, as evidenced in pediatric patients surviving bronchopulmonary dysplasia, who show persistent long-term airway dysfunction despite relatively normal alveolar gas exchange. These key concepts of compensatory lung growth are broadly applicable to other therapeutic approaches for stimulating lung growth in chronic disease or augmenting repair after injury.

Also in the November issue, in a mini-review entitled "Vascular remodeling in the circulations of the lung," Drs. E. Wagner and W. Mitzner discuss the two circulations of the lung. A unique property of the lung is that it receives both pulmonary and systemic blood flow, and a major difference between these two circulations is their capacity for angiogenesis. Whereas angiogenesis in the pulmonary circulation is quite limited, the bronchial circulation has a prolific capacity to create new blood vessels. Recognizing the impact of these differences in angiogenic capacity may allow for more focused probing of the molecular signaling that regulates angiogenic processes in the lung.

In the December issue, in a mini-review entitled "Cellular and molecular mechanisms involved in branching morphogenesis of the Drosophila tracheal system," Dr. M. Affolter and colleagues address several parallels in the development of the respiratory organs of insects and mammals. Branching morphogenesis has been studied extensively in the Drosophila tracheal system, at both the genetic and cellular levels. Past studies have shown that the branching process relies on cell migration and rearrangements, and numerous genes controlling important aspects of these two processes have been identified and analyzed. Given the documented similarities in the genetic basis of organ formation, these investigators propose that the results of studies in simple invertebrate models such as Drosophila might help to further our understanding of the more complex vertebrate organ systems.

Finally, in a Historical Perspectives article entitled "Alveolization of the lung-a history of its concepts" Dr. P. Burri reviews the various conceptions of alveolization published within the past 100 years. Alveolization of the lung has long been a subject of interest, and numerous publications within the past century have dealt with such problems as alveolar numbers, timing of alveolar formation in various species, and structural principles of alveolization. Dr. Burri describes the progress made toward understanding how alveoli are formed in the lung and, to this effect, explains the structural prerequisites and mechanisms for the emergence of new interalveolar walls. He also notes that the question of alternative mechanisms for alveolar multiplication requires clarification. Recent observations in marsupials have necessitated an expansion of the classical concept of alveolization, which may thereby necessitate revisions to current terminology.

As with all Highlighted Topics series, the Associate Editors and I hope that this series of invited mini-reviews and original research has served to promote work aimed at understanding the mechanisms of lung growth and repair, and we welcome the publication of future work in this valuable area of research in the Journal of Applied Physiology.

Gary C. Sieck

Journal of Applied Physiology, October 2004, Volume 97

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