Abstract
BackgroundRab38 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab38 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells.MethodsA replication-deficient recombinant adenovirus expressing rat Rab38 (Ad-Rab38) was constructed. Alveolar type II cells were isolated from the LEC rats and tested for lung surfactant phosphatidylcholine secretion. The rats were also examined whether exogenous expression of Ad- Rab38 could rescue the altered lung surfactant homeostasis in the lungs.ResultsIsolated type II cells infected with Ad-Rab38 exhibited improved secretion patterns of [3H]phosphatidylcholine, i.e. increased basal hyposecretion and decreased agonist-induced hypersecretion. Endobronchial administration of Ad-Rab38 improved the morphology of type II cells and lamellar bodies, reducing their sizes close to those of wild-type rats. The increased amounts of phosphatidylcholine and surfactant protein B in the lamellar body fractions were decreased in the Ad-Rab38 infected lungs.ConclusionsThese results provide strong evidence that the aberrant lung surfactant homeostasis in the LEC rats is caused by Rab38 deficit, and suggest that endobronchial delivery of the responsive transgene could be an effective method to ameliorate the abnormal lung phenotype in the animal model of HPS.
Highlights
Rab38 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells
Rab38deficient rats are a rat model of genetically heterogeneous Hermansky-Pudlak syndrome (HPS), which is clinically characterized by oculocutaneous albinism, bleeding diathesis, and in the majority of cases fatal interstitial pneumonia [5,6,7]
The goal of this study was to investigate whether adenovector-mediated endobronchial gene delivery of Rab38 into the lungs could improve aberrant lung surfactant homeostasis in the Long Evans Cinnamon (LEC) rats
Summary
Rab small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells. Rab38deficient rats are a rat model of genetically heterogeneous Hermansky-Pudlak syndrome (HPS), which is clinically characterized by oculocutaneous albinism, bleeding diathesis, and in the majority of cases fatal interstitial pneumonia [5,6,7]. These rats include several Long Evans rat sub-strains carrying the phenotype of oculocutaneous albinism and bleeding diathesis. Hydrophobic surfactant constituents were increased in lung tissues and lamellar bodies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
