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Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice

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Neural Regeneration Research 2021年第7期16卷 1258-1265页

作者： Ayaka Sugeno Wenhui Piao Miki Yamazaki Kiyofumi Takahashi Koji Arikawa Hiroko Matsunaga Masahito Hosokawa Daisuke Tominaga Yoshio Goshima Haruko Takeyama Toshio Ohshima Laboratory for Molecular Brain Science Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Biomolecular Engineering Laboratory Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Computational Bio Big-Data Open Innovation Laboratory(CBBD-OIL) National Institute of Advanced Industrial Science and Technology(AIST)TokyoJapan Research Organization for Nano and Life Innovation Waseda UniversityTokyoJapan Institute for Advanced Research of Biosystem Dynamics Waseda Research Institute for Science and EngineeringGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology(AIST)TsukubaJapan Department of Molecular Pharmacology and Neurobiology Graduate School of MedicineYokohama City UniversityYokohamaJapan

Recent studies have shown that mutation at Ser522 causes inhibition of collapsin response mediator protein 2(CRMP2) phosphorylation and induces axon elongation and partial recovery of the lost sensorimotor function after spinal cord injury(SCI).We aimed to reveal the intracellular mechanism in axotomized neurons in the CRMP2 knock-in(CRMP2KI) mouse model by performing transcriptome analysis in mouse sensorimotor cortex using micro-dissection punching system.Prior to that, we analyzed the structural pathophysiology in axotomized or neighboring neurons after SCI and found that somatic atrophy and dendritic spine reduction in sensorimotor cortex were suppressed in CRMP2KI mice.Further analysis of the transcriptome has aided in the identification of four hemoglobin genes Hba-a1, Hba-a2, Hbb-bs, and Hbb-bt that are significantly upregulated in wild-type mice with concomitant upregulation of genes involved in the oxidative phosphorylation and ribosomal pathways after SCI.However, we observed substantial upregulation in channel activity genes and downregulation of genes regulating vesicles, synaptic function, glial cell differentiation in CRMP2KI mice.Moreover, the transcriptome profile of CRMP2KI mice has been discussed wherein energy metabolism and neuronal pathways were found to be differentially regulated.Our results showed that CRMP2KI mice displayed improved SCI pathophysiology not only via microtubule stabilization in neurons, but also possibly via the whole metabolic system in the central nervous system, response changes in glial cells, and synapses.Taken together, we reveal new insights on SCI pathophysiology and the regenerative mechanism of central nervous system by the inhibition of CRMP2 phosphorylation at Ser522.All these experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee at Waseda University, Japan(2017-A027 approved on March 21, 2017;2018-A003 approved on March 25, 2018;2019-A026 approved on March 25, 2019).

关键词： CNS regeneration cortex CRMP2 hemoglobin metabolic pathway spinal cord injury spine transcriptome

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Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

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International Journal of Ophthalmology(English edition) 2015年第1期8卷 1-10页

作者： Junmi Tanaka Hideo Tanaka Nobuhisa Mizuki Eiichi Nomura Norihiko Ito Naoko Nomura Masayuki Yamane Tomonobu Hida Yoshio Goshima Hiroshi Hatano Hisashi Nakagawa Department of Ophthalmology and Visual Science Graduate School of MedicineYokohama City University Department of Ophthalmology Graduate School of MedicineUniversity of Tokyo Department of Obstetrics and Gynecology School of MedicineKeio University Department of Environmental Immuno-Dermatology Graduate School of MedicineYokohama City University Hatano Eye Clinic 438-1 FujisawaFujisawa Kanagawaken 251-0052Japan Tokushima Eye Clinic 1-2-14 Fujimi-choHigashimurayamaTokyo 189-0024Japan

AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.CONCLUSION: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

关键词： Semaphorin 3A experimental allergic conjunctivitis eosinophil infiltration serum total Ig E cytokines instillation subconjunctival administration

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Expression of semaphorin and related proteins in the fetal developing lungs: an immunohistochemical study

Expression of semaphorin and related proteins in the fetal d...

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ThirdCongressoftheAsian...

作者： Takaaki Ito Naoko Udaka Hitoshi Kitamura Masako Moezono Yukio Sasaki Yoshio Goshima Departments of Pathology Yokohama City University School of Medicine. Yokohama 236-0004Japan Departments of Pathology Yokohama City University School of Medicine. Yokohama 236-0004Japan Departments of Pathology Yokohama City University School of Medicine. Yokohama 236-0004Japan Pharmacology Yokohama City University School of Medicine. Yokohama 236-0004 Japan Pharmacology Yokohama City University School of Medicine. Yokohama 236-0004 Japan Pharmacology Yokohama City University School of Medicine. Yokohama 236-0004 Japan

＜正＞The semaphorin （Sema）/collapsin family of molecules plays an important role in axonal pathfinding during neuronal development by inhibiting growth cone extension.Sema is expressed in non-neuronal tissues inclu...

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