title: Comparative analysis of the mechanical signals in lung development and compensatory growth.
abstract: This review compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. Re-initiation of anatomical lung growth in the mature lung is possible when the loss of functioning lung units renders the existing physiologic-structural reserves insufficient for maintaining adequate function and physical stress on the remaining units exceeds a critical threshold. The appropriate spatial and temporal mechanical interrelationships and the availability of intra-thoracic space, are crucial to growth initiation, follow-on remodeling and physiological outcome. While the endogenous potential for compensatory lung growth is retained and may be pharmacologically augmented, supra-optimal mechanical stimulation, unbalanced structural growth, or inadequate remodeling may limit functional gain. Finding ways to optimize the signal-response relationships and resolve structure-function discrepancies are major challenges that must be overcome before the innate compensatory ability could be fully realized. Partial pneumonectomy reproducibly removes a known fraction of functioning lung units and remains the most robust model for examining the adaptive mechanisms, structure-function consequences and plasticity of the remaining functioning lung units capable of regeneration. Fundamental mechanical stimulus-response relationships established in the pneumonectomy model directly inform the exploration of effective approaches to maximize compensatory growth and function in chronic destructive lung diseases, transplantation and bioengineered lungs.
authors.affiliation: Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, 5323 Harry Hines Blvd., Dallas, TX, 75390-9034, USA. Connie.Hsia@utsouthwestern.edu.
authors.forename: Connie C W
authors.initials: CC
authors.lastname: Hsia
mesh_terms: D000818:Animals; D008168:Lung / Q000254:growth & development* / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D012038:Regeneration; D015398:Signal Transduction; D057170:Translational Research, Biomedical
keywords: Lung development; Lung regeneration; Mechanical stress; Mechanotransduction; Pneumonectomy