Contributions of Retinoids to the Generation and Repair of the Pulmonary Alveolus: RA
Studies using cultured LIF indicate that the levels of RAR-p and RAR-7 increase at birth, at the same time that these cells contain their maximal amount of RA.9 The increase in RAR-7 was transient, decreasing after postnatal day 2 (when endogenous LIF RA also decreases), suggesting that RA may signal transiently through RAR-7 to influence cellular function in the early postnatal period. To examine this issue further, we studied mice bearing a null deletion for the RAR-7 gene. Because RARs heterodimerize with RXRs prior to the binding of the heterodimeric complex to DNA, we also examined mice heterozygous for the RXR-a gene deletion. Homozygous, null RXR-a mice die in utero from cardiac malformations. Mice bearing the null deletion of RAR-7 and heterozygote for the RXR-a deletion (RAR-7-/-, RXR-a+/-) demonstrate a decrease in elastin gene expression in the LIF at postnatal day 10 and a decrease in elastic tissue in the lung at postnatal day 28. Allergy treatment Here The decrement in elastic fibers was limited to the alveolar septa and did not occur in the airway or vascular walls. Morphometric analysis of alveolar architecture demonstrated that the compound deletion of RAR-7 and RXR-a resulted in approximately twofold fewer alveoli and a similar decrease in alveolar surface area. Mice bearing only the RAR-7 gene deletion demonstrated a decrease in alveolar number and surface area that was intermediate between that of the wild-type and the RAR-^-/-, RXR-a+/-mice. This decrement was accompanied by changes in the physiologic properties of the distal lungs of these mice.
The static compliance of the lung was increased by the RAR-7-/- gene deletion. Preliminary data indicate that the decrease in alveolar surface area is accompanied by a decrease in the diffusion of carbon monoxide in mice bearing the RAR-7 gene deletion.