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Role of cell cycle‐associated proteins in microglial proliferation in the axotomized rat facial nucleus
Author(s) -
Yamamoto Shinichi,
Kohsaka Shinichi,
Nakajima Kazuyuki
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22291
Subject(s) - cyclin a , cyclin a2 , biology , cyclin dependent kinase , cyclin e , cyclin d , microbiology and biotechnology , cyclin , cell cycle , microglia , cyclin b , cancer research , cyclin dependent kinase 2 , kinase , protein kinase a , immunology , biochemistry , apoptosis , inflammation
Abstract We analyzed cell cycle‐associated proteins, including cyclins, cyclin‐dependent protein kinases (Cdks), and Cdk inhibitors (CdkIs) in the axotomized rat facial nucleus. Immunoblotting revealed that cyclin A and cyclin D are induced 3–5 days after transection. The induced cyclin A was immunohistochemically recognized in microglia. Cdk2 and Cdk4 were also detected in the facial nucleus. The CdkI p21 was elevated 5 days after axotomy. Inhibition experiments in vitro using a cFms (receptor for macrophage‐colony stimulating factor, M‐CSF) inhibitor indicated that M‐CSF‐cFms signaling leads to upregulation of the levels of cyclin A, cyclin D, proliferating cell nuclear antigen (PCNA), and cFms in microglia. The role of cyclin A/Cdk2 activity in M‐CSF‐dependent microglial proliferation was ascertained using the specific inhibitor purvalanol A. Experiments using specific mitogen‐activated protein kinase inhibitors suggested that c‐Jun N‐terminal kinase (JNK) is associated with M‐CSF‐dependent induction of cyclins and PCNA, whereas p38 is associated with cFms induction. Both JNK and p38 were proved to be phosphorylated by stimulation with M‐CSF. Our results indicated that cyclin A, cyclin D, Cdk2, Cdk4, and p21 are involved in microglial proliferation in the transected facial nucleus, and that the M‐CSF‐dependent upregulations of cyclins/PCNA and cFms in microglia are differentially regulated by JNK and p38. © 2012 Wiley Periodicals, Inc.