Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous retinoids have been implicated in alveologenesis in both the rat and the mouse, and exogenous retinoic acid (RA) can reverse or partially reverse experimental emphysema in adult rat and mouse models by an unknown mechanism. In this study, we examine the cellular and molecular biology of retinoid signaling during alveologenesis in the mouse. We describe the temporal and spatial expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT-PCR and immunohistochemistry. We identify the retinoic acid receptor isoforms RAR-alpha 1, RAR-beta 2, RAR-beta 4, and RAR-gamma 2 and describe their temporal and spatial expression using RT-PCR and in situ hybridization. We demonstrate that both retinoid binding proteins and RAR isoforms are temporally regulated and found within the alveolar septal regions during alveologenesis. These data support a role of dynamic endogenous RA signaling during alveolar formation.
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PMID:Temporal/spatial expression of retinoid binding proteins and RAR isoforms in the postnatal lung. 1183 40

A technically easy, noninvasive means of delivering molecules to alveoli, which act selectively or specifically in the lung, would be experimentally and therapeutically useful. As proof of principle, we took advantage of the spreading ability of pulmonary surface active material (InfaSurf), mixed it with elastase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) small inhibitory RNA (siRNA), or all-trans retinoic acid (ATRA), and instilled microliter amounts of the mixture into the nose of lightly anesthetized mice. One instillation of elastase caused diffuse alveolar destruction (emphysema) demonstrating widespread alveolar delivery. A single nasal instillation of GAPDH siRNA, compared with scrambled GAPDH siRNA, lowered GAPDH protein in lung, heart, and kidney by approximately 50-70% 1 and 7 days later. To test the possibility of lung-specific delivery of a potentially therapeutic drug, we administered ATRA and monitored its effect on expression of cellular retinol binding protein (CRBP)-1 mRNA, whose translation product is a key molecule in retinoid metabolism. Given intranasally, ATRA elevated CRBP-1 mRNA 4.3-fold in a lung-specific manner. The same dose and dose schedule of ATRA given intraperitoneally increased CRBP-1 mRNA only approximately 1.8-fold in lung; intraperitoneally administered ATRA elevated expression of CRBP-1 mRNA 1.7-fold or more in brain cortex, cerebellum, and testes, thereby increasing the risk of untoward effects. This simple noninvasive technique allows regulation of specific proteins in the lung and lung-specific delivery of reagents of experimental and potentially therapeutic importance.
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PMID:Noninvasive delivery of small inhibitory RNA and other reagents to pulmonary alveoli in mice. 1523 6