Enhanced proliferation of astrocytes from beta(2)-adrenergic receptor knockout mice is influenced by the IGF system.
In the present study, we investigated the IGF system in neonatal astrocytes derived from mice with a targeted disruption of the beta-2 adrenergic receptor (beta(2)AR). beta(2)AR knockout astrocytes demonstrated higher proliferation rates and increased expression of the astrogliotic marker GFAP, as compared with wild-type cells. beta(2)AR deletion also regulated molecules of the IGF system. Although IGF-1 levels remained unaltered, IGF-2 and type 1 IGF receptor expression was increased in beta(2)AR knockout cells. Furthermore, conditioned medium from knockout astrocytes contained lower levels of IGF binding protein-2 and -4. Our data suggest a deficit of beta(2)AR on astrocytes, as previously reported in multiple sclerosis, may have implications on proliferative status of astrocytes, a feature that might be attributed to regulation of IGF mitogenic actions.
Chesik
Daniel
D
Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands. d.chesik@med.umcg.nl
Glazenburg
Lisa
L
De Keyser
Jacques
J
Wilczak
Nadine
N
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D017077:Culture Media, Conditioned; D018970:Insulin-Like Growth Factor Binding Protein 1; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D018343:Receptors, Adrenergic, beta-2; D017526:Receptor, IGF Type 1