Contributions of Retinoids to the Generation and Repair of the Pulmonary Alveolus: Conclusion
In summary, RAR-^-/-mice demonstrate biochemical, anatomic and physiologic characteristics of emphysema at postnatal week 4. The time course of the development of the emphysematous phenotype is similar to that observed in the tight-skinned mouse, another genetic model of congenital emphysema resulting from a duplication within the coding region of the fibrillin-1 gene.11 These data indicate that retinoids are involved in alveolar formation and that elastin is one of the target genes.
Future Considerations for Evaluating a Role for Treatment of Emphysema With Retinoids
While elastin gene expression is required for alveolar formation, our data do not establish this as the only or the primary source of the abnormalities observed by interrupting RA-mediated signaling during alveolar development. It is likely that other genes are also influenced by retinoids, and alterations of elastin expression may be secondary to a more generalized effect on cellular proliferation or differentiation More info buy claritin online. Among the other genes that may be targets of retinoid action that may secondarily alter elastin gene expression are the growth factors, transforming growth factor-p and platelet-derived growth factor-a and its receptor. Other potential targets are the nuclear receptors for home-odomain proteins, such as Hox B5 and GATA family members such as GATA-4, GATA-5, and GATA-6. Our future goals include identifying better markers of the pulmonary myofibroblast phenotype, identifying mechanisms that regulate LIF proliferation, migration, and differentiation, and to evaluate the interstitial myofibroblast phenotype during emphysema.
Other important questions that must be addressed to establish the clinical utility of retinoids in the treatment of emphysema include the following: (1) can selective retinoids be targeted to specific cellular events to achieve the desired effects without toxicity, and (2) how can the duration of administration of potentially deleterious compounds be limited in a slowly progressive disease?