TY - JOUR
T1 - Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin
AU - Ikeshima-Kataoka, Hiroko
AU - Abe, Yoichiro
AU - Abe, Takaya
AU - Yasui, Masato
N1 - Funding Information:
The authors thank Dr. Shinichi Kohsaka and Dr. Keiko Ohsawa at Department of Neurochemistry, National Institute of Neuroscience for the kind suggestion for microglial analysis, and Dr. Mayumi Kajimura at Department of Biochemistry, Keio University School of Medicine for kindly permitting us to use vibratome (Leica Microsystems), and Ms. Motoko Furukawa, Ms. Sayaka Inui and Ms. Manae Imamura for their technical supports. This work was supported by the Global Center of Excellence Program for Humanoid Metabolomic Systems Biology of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan , Grant-in-Aid for Scientific Research B (General) of MEXT of Japan and the Japan New Energy and Industrial Technology Development Organization (NEDO) .
PY - 2013/9
Y1 - 2013/9
N2 - During injury to the central nervous system (CNS), astrocytes and microglia proliferate and migrate around the lesion sites. Recently, it has been reported that one of the water channels, aquaporin-4 (AQP4) is seemed to have a role in astroglial migration and glial scar formation caused by brain injury, although its molecular mechanism is largely unknown. In the present study, we examined the expression profiles in wild-type (WT) and AQP4-deficient (AQP4/KO) mice after a stab wound to the cerebral cortex. Three days after the stab wound, AQP4 expression was observed in activated microglia around the lesion site as well as in astrocytes. A microarray analysis revealed that 444 genes around the lesion site were upregulated 3. days after the wounding in WT mice. Surprisingly, most of these up-regulations were significantly attenuated in AQP4/KO mice. Real-time RT-PCR and immunofluorescence showed that osteopontin (OPN) expression around the lesion site was much lower in AQP4/KO mice than in WT mice. Moreover, the up-regulation of pro-inflammatory cytokines was significantly attenuated in AQP4/KO mice. Taken together, these results suggest that AQP4 plays an important role in immunological function in concert with OPN under pathological conditions in the CNS.
AB - During injury to the central nervous system (CNS), astrocytes and microglia proliferate and migrate around the lesion sites. Recently, it has been reported that one of the water channels, aquaporin-4 (AQP4) is seemed to have a role in astroglial migration and glial scar formation caused by brain injury, although its molecular mechanism is largely unknown. In the present study, we examined the expression profiles in wild-type (WT) and AQP4-deficient (AQP4/KO) mice after a stab wound to the cerebral cortex. Three days after the stab wound, AQP4 expression was observed in activated microglia around the lesion site as well as in astrocytes. A microarray analysis revealed that 444 genes around the lesion site were upregulated 3. days after the wounding in WT mice. Surprisingly, most of these up-regulations were significantly attenuated in AQP4/KO mice. Real-time RT-PCR and immunofluorescence showed that osteopontin (OPN) expression around the lesion site was much lower in AQP4/KO mice than in WT mice. Moreover, the up-regulation of pro-inflammatory cytokines was significantly attenuated in AQP4/KO mice. Taken together, these results suggest that AQP4 plays an important role in immunological function in concert with OPN under pathological conditions in the CNS.
KW - AQP4
KW - Astrocytes
KW - Microarray
KW - Microglia
KW - OPN
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U2 - 10.1016/j.mcn.2013.02.002
DO - 10.1016/j.mcn.2013.02.002
M3 - Article
C2 - 23428384
AN - SCOPUS:84876311563
SN - 1044-7431
VL - 56
SP - 65
EP - 75
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
ER -