A01

蚊の腸上皮レジリエンスを支える二面ECMの機能解明

Dual-Sided ECMs as a Foundation for Epithelial Resilience in the Mosquito Midgut

腸管上皮は，管腔内容物の変動や持続的な機械的負荷にさらされながらも，極性とバリア機能を維持する高いレジリエンスを示す．しかし，このような上皮の頑健性が細胞外マトリックス（ECM）との相互作用によってどのように支えられているのかは，十分に理解されていない．吸血性節足動物である蚊の中腸は，吸血時に短時間で急激に膨張し，その後収縮して元の状態へと回復する．この大規模な可逆的変形は，上皮組織が極端な力学環境に適応する仕組みを解析するうえで有用なモデルである．本研究では，管腔側の囲食膜と基底側の基底膜という，上皮を二面から支えるECMに着目する．これら二つのECMが，上皮の極性維持，伸展・収縮，バリア機能をどのように協調的に制御するのかを明らかにするため，ECMの形成，配置，物性の時空間的変化を解析し，上皮細胞応答との関係を統合的に検討する．本研究により，極端な変形に耐える上皮レジリエンスの基本原理の解明を目指す．

The intestinal epithelium exhibits remarkable resilience, maintaining its polarity and barrier function despite being subjected to fluctuating luminal contents and continuous mechanical loads. However, the mechanisms by which interactions with the extracellular matrix (ECM) support this epithelial robustness remain poorly understood. The midgut of the mosquito, a blood-feeding arthropod, undergoes rapid and drastic expansion during a blood meal, subsequently contracting to return to its original state. This large-scale reversible deformation serves as an excellent model for analyzing how epithelial tissues adapt to extreme mechanical environments. In this study, we focus on the two types of ECM that support the epithelium from both sides: the peritrophic matrix on the luminal side and the basement membrane on the basal side. To elucidate how these two ECMs coordinately regulate epithelial polarity, expansion/contraction, and barrier function, we will analyze the spatiotemporal changes in ECM formation, arrangement, and physical properties, and integrate these findings with epithelial cell responses. Through this research, we aim to uncover the fundamental principles of epithelial resilience that enable tissues to withstand extreme deformation.