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In vivo血液脳関門ECMの再構成に基づくin vitro血液脳関門培養系の最適化
Optimization of in vitro Blood-Brain Barrier Culture System Based on Reconstruction of in vivo Blood-Brain Barrier ECM


内田 康雄  (広島大学 医系科学研究科, 教授) 

Yasuo Uchida (Hiroshima Univ.)

Figure_A02_HiroshimaUniv_Uchida - 内田康雄.jpg

我々は, 豊富なヒト脳組織を使用できる強みを活かして, てんかん, アルツハイマー病, 脳アミロイド血管症, 多発性硬化症など多くの中枢疾患で, 血液脳関門(BBB)の細胞外マトリックス(ECM)構成タンパク質の存在量が多様に変動することによってBBBの密着結合が崩壊することを見出しつつある. 従って, ECMの質的・量的な組成を正常化することが, BBBの密着結合の形成・維持に必須である. そこで, 本研究では, 独自のquantitative Global Absolute Proteomics (qGAP)法を用いて, ヒトの正常のin vivo BBBの細胞外マトリックス(ECM)構成タンパク質の絶対存在量を正確かつ網羅的に解明し, in vitro BBB培養系のそれらと比べたときの差分(In vitro BBB培養系で不足している種類と量)を定量的に解明することを目的とする. さらに, in vivoのECM環境の再構築を試みることによって, 密着結合の形成の分子機構を詳細に理解する.

Taking advantage of the availability of abundant human brain tissue, we are finding that, in many central nervous system diseases such as epilepsy, Alzheimer's disease, cerebral amyloid angiopathy and multiple sclerosis, the tight junction at the blood-brain barrier is disrupted by diverse variations in the abundance of extracellular matrix (ECM) proteins at the BBB. Therefore, it would be essential to qualitatively and quantitatively recover the pathological compositions of the ECM to normal compositions in order to normally form and maintain the tight junctions at the BBB. In the present study, we will use the original quantitative Global Absolute Proteomics (qGAP) method to accurately and comprehensively elucidate the absolute abundance of ECM proteins at normal human in vivo BBB, and to determine their differential abundance compared to those of in vitro BBB culture systems. Furthermore, by attempting to reconstruct the in vivo ECM environment, the molecular mechanisms of tight junction formation would be understood in detail.

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