Seminar: “Retinol Binding Protein 4 (RBP4) and Cell Surface Signaling Receptor and Transporter of Retinol (STRA6) in Acute Lung Injury” - Ibrahim Dar

Endocrinology and Animal Biosciences Thesis Defense Seminar

Ibrahim Dar
MS Student
Graduate Program in Endocrinology and Animal Biosciences

Retinoids (vitamin A and its metabolites) are essential lipid components of the alveolar microenvironment, and cell-type-specific retinoid metabolism is required to maintain the functional health of the adult lung. Retinoid actions in the lung are predominantly mediated through the signaling of all-trans-retinoic acid (ATRA), a transcriptionally active retinoid species, and its distinct cognate nuclear hormone receptors, retinoic acid receptors (RARα, -β, and -γ). While it is understood that intracellular ATRA actions underlie the physiological activity of retinoids in the lung, including immunity and inflammatory responses during injuries, the physiological processes upstream of ATRA synthesis, including retinoid delivery to lung cells and the pathways that enable these cells to acquire retinoids, remain poorly understood. The prevailing paradigm is that the RBP4-STRA6 axis is the primary route of retinoid delivery to extrahepatic tissues, however the functional involvement of this pathway in retinoid delivery to the lung has not been systematically studied. Using genetically manipulated animal models lacking functional RBP4 (Rbp4-/- mice) or STRA6 (Stra6-/- mice), our studies demonstrate that in the normal healthy adult lung, the RBP4-STRA6 axis does not significantly contribute to physiological retinoid delivery in vivo. However, the RBP4-STRA6 pathway may be activated in lung tissue during experimentally induced acute lung injury (ALI), driven by STRA6 upregulation at early stages, followed by RBP4 upregulation at later stages, particularly in immune cells infiltrating the injured lung. Furthermore, we provide experimental evidence that the RBP4-STRA6 axis regulates the extent of the acute inflammatory response, lung function, and survival during ALI. Importantly, our findings suggest that the RBP4-STRA6 axis is a target for pharmacological interventions aimed at reducing ALI severity and improving survival and recovery.