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Microglial cell cycle‐associated proteins control microglial proliferation in vivo and in vitro and are regulated by GM‐CSF and density‐dependent inhibition
Author(s) -
Koguchi Ken,
Nakatsuji Yuji,
Okuno Tatsusada,
Sawada Makoto,
Sakoda Saburo
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10829
Subject(s) - microbiology and biotechnology , microglia , cell cycle , downregulation and upregulation , biology , cyclin , cyclin d1 , cell growth , in vivo , cyclin d , cancer research , chemistry , immunology , cell , biochemistry , inflammation , gene
Hyperplasia of microglia is one characteristic of reactive gliosis, which is observed in various pathologic conditions in the central nervous system (CNS). To investigate the regulation mechanisms of microglial proliferation, the effect of granulocyte macrophage colony‐stimulating factor (GM‐CSF) on the expression of cell cycle‐associated proteins was examined in the microglial cell line GMI‐M6‐3. After GM‐CSF administration, cyclins D1, E, and A and cyclin‐dependent kinase inhibitor p21 Cip1 were increased, and another cyclin‐dependent kinase inhibitor, p27 Kip1 , was decreased with morphologic transformation into ameboid form. By contrast, downregulation of these cyclins and p21 Cip1 , and strong upregulation of p27 Kip1 accompanied by ramification were observed with GM‐CSF deprivation. We also found that GMI‐M6‐3 exhibited homotypic contact inhibition of proliferation without any morphologic transformation. The increase of p27 Kip1 and the decrease of cyclin A were suggested to play an important role in microglial contact inhibition. In addition, the direct effect of p27 Kip1 to inhibit microglial proliferation was demonstrated both in vitro and in vivo by overexpression of p27 Kip1 . © 2003 Wiley‐Liss, Inc.