Thinning, septation, and change in cellular composition of the saccules that compose the gas-exchange region of the immature lung, and the postseptation increase in alveolar number and average alveolar volume, effect the relation between the gas-exchange surface area (Sa) and the organism's metabolic rate (VO2). Our studies demonstrate, or are consistent with, the following new information and ideas: 1) means """"""""other"""""""" than septation produce most alveoli formed during the period of """"""""septation""""""""; 2) dexamethasone (Dex) treatment during septation irrevocably blocks septation, and slows the rate of """"""""other"""""""" means of forming alveoli even after Dex-treatment is stopped; 3) the Dex-induced effects include the premature completion of the seemingly normal changes in the relative cellular composition of the alveolar wall; 4) clinically relevant short- term prenatal treatment with Dex does not affect Sa at birth but is expressed as diminished postnatal increase in Sa; 5) thyroid hormone, in doses that do not increase VO2, accelerates the postnatal increase of Sa. We will continue to take advantage of new stereological methods to: 1) test the hypothesis that short-term (3 days) Dex treatment in late gestation or during the period of """"""""septation"""""""" can prematurely and permanently terminate (or diminish) septation or """"""""other"""""""" means of forming alveoli and that this effect occurs with premature completion of the normal developmental evolution of the absolute cellular composition of the gas- exchange wall; 2) determine the architectural mechanism by which thyroid hormone, in non-calorigenic doses, accelerates the early postnatal increase in Sa, elucidate its effect on the cellular composition of the gas-exchange wall (contrasting it with the effect of Dex), and, test if thyroid hormone can overcome the Dex-impairment of alveolus formation and increase of Sa; 3) """"""""mark"""""""" already formed lung to test if, after septation, new alveolus formation occurs mainly at the alveolar-pleural interface. We think our prior results show the feasibility of our approach, and, the strong likelihood we will provide substantial new insights into a neglected but physiologically and clinically important aspect of lung development.
| Clerch, Linda Biadasz; Baras, Alex S; Massaro, Gloria DeCarlo et al. (2004) DNA microarray analysis of neonatal mouse lung connects regulation of KDR with dexamethasone-induced inhibition of alveolar formation. Am J Physiol Lung Cell Mol Physiol 286:L411-9 |
| Massaro, Donald; Massaro, Gloria Decarlo (2004) Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. Am J Physiol Lung Cell Mol Physiol 287:L1154-9 |
| Xiao, Hong; Massaro, Donald; Massaro, Gloria DeCarlo et al. (2004) Expression of lung uncoupling protein-2 mRNA is modulated developmentally and by caloric intake. Exp Biol Med (Maywood) 229:479-85 |
| Massaro, Donald; Massaro, Gloria DeCarlo; Baras, Alex et al. (2004) Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression. Am J Physiol Lung Cell Mol Physiol 286:L896-906 |
| Massaro, Donald; Massaro, Gloria Decarlo; Clerch, Linda Biadasz (2004) Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice. Am J Physiol Lung Cell Mol Physiol 287:L1066-70 |
| Dirami, Ghenima; Massaro, Gloria DeCarlo; Clerch, Linda Biadasz et al. (2004) Lung retinol storing cells synthesize and secrete retinoic acid, an inducer of alveolus formation. Am J Physiol Lung Cell Mol Physiol 286:L249-56 |
| Massaro, Donald; Massaro, Gloria DeCarlo (2004) Critical period for alveologenesis and early determinants of adult pulmonary disease. Am J Physiol Lung Cell Mol Physiol 287:L715-7 |
| Massaro, Gloria DeCarlo; Massaro, Donald; Chambon, Pierre (2003) Retinoic acid receptor-alpha regulates pulmonary alveolus formation in mice after, but not during, perinatal period. Am J Physiol Lung Cell Mol Physiol 284:L431-3 |
| Massaro, Donald; Massaro, Gloria DeCarlo (2003) Retinoids, alveolus formation, and alveolar deficiency: clinical implications. Am J Respir Cell Mol Biol 28:271-4 |
| Massaro, Gloria DeCarlo; Radaeva, Svetlana; Clerch, Linda Biadasz et al. (2002) Lung alveoli: endogenous programmed destruction and regeneration. Am J Physiol Lung Cell Mol Physiol 283:L305-9 |
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