title: Clusterin enhances proliferation of primary astrocytes through extracellular signal-regulated kinase activation.
abstract: Clusterin, a secretory glycoprotein, has been shown to be up-regulated in the reactive astrocytes in response to brain injury and neurodegenerative diseases, but its function has not been clearly elucidated. In this study, we investigate whether clusterin has growth-stimulatory activity in astrocytes. Suppression of clusterin with antisense oligonucleotide induced growth arrest, whereas transient overexpression of clusterin by cDNA transfection or exogenous treatment with purified clusterin promoted proliferation of the primary astrocytes in culture. This clusterin-stimulated proliferation was abrogated by PD98059, an inhibitor of mitogen-activated protein kinase kinase. These results suggest that clusterin might play an important role in astrogliosis by stimulating the proliferation of astrocytes through activation of the extracellular signal-regulated kinase 1/2 signaling pathway.
authors.affiliation: Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Shin
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shim
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Byeong-Moo
authors.initials: BM
authors.lastname: Kim
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Kee
authors.forename: Joong-Jean
authors.initials: JJ
authors.lastname: Park
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Bon-Hong
authors.initials: BH
authors.lastname: Min
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051152:Clusterin / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014316:Tritium / Q000378:metabolism
chemical_list: D051152:Clusterin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020319:Oligodeoxyribonucleotides, Antisense; D014316:Tritium; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D013936:Thymidine