Zhongmei Zheng1,2,3, Bangrong Cao4, Yu Hu5, Liang Xie6,3, Ling Gu6,3, Fang Shi6,3, Hanmin Liu7,8,9. 1. Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, 610041, China. 2. Department of Pediatrics, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 3. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China. 4. Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 5. Department of Pediatrics, Mianyang Central Hospital, Mianyang, China. 6. The Vascular Remodeling and Developmental Defects Research Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China. 7. Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, 610041, China. liuhm@scu.edu.cn. 8. The Vascular Remodeling and Developmental Defects Research Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China. liuhm@scu.edu.cn. 9. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China. liuhm@scu.edu.cn.
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.
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.
Authors: Sarah J Horvat; Deepak A Deshpande; Huandong Yan; Reynold A Panettieri; Juan Codina; Thomas D DuBose; Wenkuan Xin; Thomas C Rich; Raymond B Penn Journal: FASEB J Date: 2012-05-30 Impact factor: 5.191
Authors: Matthias C Hütten; Markus Fehrholz; Franziska M Konrad; Daan Ophelders; Clementine Kleintjes; Barbara Ottensmeier; Owen Brad Spiller; Kirsten Glaser; Boris W Kramer; Steffen Kunzmann Journal: J Aerosol Med Pulm Drug Deliv Date: 2019-10-01 Impact factor: 2.849