title: β2-Adrenoreceptor-Mediated Proliferation Inhibition of Embryonic Pluripotent Stem Cells.
abstract: Adrenoreceptors (ARs) are widely expressed and play essential roles throughout the body. Different subtype adrenoceptors elicit distinct effects on cell proliferation, but knowledge remains scarce about the subtype-specific effects of β2-ARs on the proliferation of embryonic pluripotent stem (PS) cells that represent different characteristics of proliferation and cell cycle regulation with the somatic cells. Herein, we identified a β2-AR/AC/cAMP/PKA signaling pathway in embryonic PS cells and found that the pathway stimulation inhibited proliferation and cell cycle progression involving modulating the stem cell growth and cycle regulatory machinery. Embryonic stem (ES) cells and embryonal carcinoma stem (ECS) cells expressed functional β-ARs coupled to AC/cAMP/PKA signaling. Agonistic activation of β-ARs led to embryonic PS cell cycle arrest and proliferation inhibition. Pharmacological and genetic analyzes using receptor subtype blocking and RNA interference approaches revealed that this effect selectively depended on β2-AR signaling involving the regulation of AKT, ERK, Rb, and Cyclin E molecules. Better understanding of the effects of β2-ARs on embryonic PS cell proliferation and cycle progression may provide new insights into stem cell biology and afford the opportunity for exploiting more selective ligands targeting the receptor subtype for the modulation of stem cells.
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Pharmacy, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Fan
authors: F
authors: Sun
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xin-Jie
authors: XJ
authors: Yang
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Hao-Yu
authors: HY
authors: Lv
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Ya-Bin
authors: YB
authors: Tang
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Shi-Min
authors: SM
authors: An
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xu-Ping
authors: XP
authors: Ding
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Wen-Bin
authors: WB
authors: Li
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Lin
authors: L
authors: Teng
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Ying
authors: Y
authors: Shen
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Hong-Zhuan
authors: HZ
authors: Chen
authors: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai, China.
authors: Liang
authors: L
authors: Zhu
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D051058:Oncogene Protein v-akt