Spatiotemporal Changes in the Gene Expression Spectrum of the β2 Adrenergic Receptor Signaling Pathway in the Lungs of Rhesus Monkeys

Abstract

Objective β2 adrenergic receptor (ADRB2) agonists mainly participate in regulation of airway function through the ADRB2-G protein-adenylyl cyclase (AC) signaling pathway; however, the key genes associated with this pathway and the spatiotemporal changes in the expression spectrum of some of their subtypes remain unclear, resulting in an insufficient theoretical basis for formulating the dose and method of drug administration for neonates. Methods We performed sampling at different developmental time points in rhesus monkeys, including the embryo stage, neonatal stage, and adolescence. The MiSeq platform was used for sequencing of key genes and some of their subtypes in the ADRB2 signaling pathway in lung tissues, and target gene expression was normalized and calculated according to reads per kilobase million. Results At different lung-developmental stages, we observed expression of phenylethanolamine N-methyltransferase ( PNMT ), ADRB2 , AC, AKAP and EPAC subtypes (except AC8, AKAP4/5 ), and various phosphodiesterase ( PDE ) subtypes ( PDE3 , PDE4 , PDE7 , and PDE8 ), with persistently high expression of AC6 , PDE4B , and AKAP (1/2/ 8/9/12/13 , and EZR ) maintained throughout the lung-developmental process, PNMT , ADRB2 , AC (4/6), PDE4B, and AKAP (1/2/ 8/9/12/13, EZR, and MAP2 )were highly expressed at the neonatal stage. Conclusion During normal lung development in rhesus monkeys, key genes associated with ADRB2–G protein–AC signaling and some of their subtypes are almost all expressed at the neonatal stage, suggesting that this signaling pathway plays a role in this developmental stage. Additionally, AC6 , PDE4B , and AKAP (1/2/ 8/9/12/13, and EZR ) showed persistently high expression during the entire lung-developmental process, which provides a reference for the development and utilization of key gene subtypes in this pathway.