Contributions of Retinoids to the Generation and Repair of the Pulmonary Alveolus: Lung Explants
During the second postnatal week, they may comprise up to 25% of alveolar cells. The lipids are primarily neutral lipids that are acquired, much like adipocytes, but they also contain retinyl esters. Retinyl esters are most abundant during late gestation in the rat, and their content decreases after birth. This decrease in endogenous LIF retinyl esters is accompanied by an increase in the retinol and retinoic acid (RA) contents of these cells. We hypothesized that the endogenous LIF retinoids may influence the expression of genes in these cells and influence their ability to produce extracellular matrix proteins. To evaluate this hypothesis, we have used several strategies. First we have examined the effects of exogenous all-trans RA (ATRA) and 9-cis-RA on gene expression by cultured LIF read sildenafil citrate pink. Second we have interrupted the conversion of endogenous retinyl esters to RA and examined changes in the expression of elastin and collagen. Third, we studied mice with null deletions for various RA receptors (RAR) and retinoid X-receptors (RXR), and evaluated changes in alveolar architecture and gene expression.
Retinoids Influence Elastin Gene Expression in Cultured LIF and Lung Explants
Retinoids are chemical derivatives of all-trans retinol, commonly known as vitamin A. Vitamin A is acquired from the diet primarily as retinyl esters, linked to fatty acids such as palmitic acid, or as carotenoids that are dimers of retinal (the aldehyde oxidation product of retinol) iso-mers. Cells acquire retinol from the circulation or by hydrolyzing endogenous stores of retinyl esters. LIF utilizes both mechanisms.
Cultured LIF assumes a myofibroblast phenotype and contains desmin, myosin heavy chain, and a-actin filament proteins that are usually reserved to smooth-muscle cells.