Contributions of Retinoids to the Generation and Repair of the Pulmonary Alveolus

Contributions of Retinoids to the Generation and Repair of the Pulmonary AlveolusDuring the last 4 years, there has been a renewed interest in strategies directed at the restoration of the alveolar surface area and the respiratory and mechanical function of the lung parenchyma. Retinoids have received considerable attention as alveolar morphogens and potential therapeutic agents, after retinoic acid was shown to ameliorate the emphysema that was observed in rats after an intratracheal instillation of elastase. To better define the potential contributions of retinoids, I will summarize the work in my laboratory and by other investigators that defines how retinoids alter alveolar structure and the expression of a few selected gene products.
Alveolar architecture is dependent on the anatomy of the conducting airways that are primarily formed prior to birth in mice, rats, and humans. Airway branching, elongation, and cellular differentiation are all influenced by retinoids. However, this discussion will be limited to the process of alveolar formation that occurs largely after birth in these species. Alveolar septa are comprised of epithelial and endothelial cells, fibroblasts, and a few immune and neuroendocrine cells website The effects of retinoids have been most extensively characterized for pulmonary epithelial and mesenchymal cells. In the alveolus, the fibroblast is a major contributor to the formation of the extracellular matrix, which provides tensile strength and elasticity to the gas exchange surface. Two populations of pulmonary interstitial fibroblast have been identified morphologically, but they share many similar protein synthetic characteris-tics. The most obvious morphologic difference is the abundant lipid droplets in the lipid-laden interstitial fibroblast (LIF) subpopulation during early postnatal life, which are particularly abundant in mice and rats.