Clusterin enhances proliferation of primary astrocytes through extracellular signal-regulated kinase activation.
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.
Shin
Yong-Jae
YJ
Department of Pharmacology and BK21 Program for Medical Sciences, College of Medicine, Korea University, Seoul, Korea.
Kang
Sang-Wook
SW
Jeong
Seong-Yun
SY
Shim
Young-Jun
YJ
Kim
Youn-Hee
YH
Kim
Byeong-Moo
BM
Kee
Sun-Ho
SH
Park
Joong-Jean
JJ
Park
In-Sun
IS
Min
Bon-Hong
BH
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
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