title: Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin.
abstract: 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.
authors: Department of Pharmacology and Neuroscience, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan. Electronic address: ikeshima@z3.keio.jp.
authors: Hiroko
authors: H
authors: Ikeshima-Kataoka
authors: Yoichiro
authors: Y
authors: Abe
authors: Takaya
authors: T
authors: Abe
authors: Masato
authors: M
authors: Yasui
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014951:Wounds, Stab / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D053495:Osteopontin
keywords: AQP4; Astrocytes; CNS; IL-1β; Microarray; Microglia; OPN; TNF-α; aquaporin-4; central nervous system; interleukin 1β; osteopontin; tumor necrosis factor-α