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Dec 7th 

Research Presentations



 Macrophage-to-myofibroblast transition involved in UUO induced cardiac fibrosis


Xiaomeng Gao, Panpan Qiang, Yutong Han, Yunzhao Xiong, Qingyou Xu and Tatsuo Shimosawa

    Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China

    Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita, Japan

 The formation of cardiorenal syndrome is closely related to the disorder of neurohumoral metabolism. Obstructive nephropathy such as UUO can activate RAS system, induce MR activation, and induce inflammatory injury to participate in the process of cardiac fibrosis.

   Male Wistar rats with UUO to induce obstructive nephropathy, and the mineralocorticoid receptor blocker eplerenone (100mg/Kg/D) was given at the same time. After 6 months, the function and structural changes of the kidney and heart were observed.

    The results showed that the renal function of the rats was damaged and the fibrosis changes had showed in contralateral kidney, the enlarged heart and impaired heart function especially the diastolic function, a large number of inflammatory cell infiltration and cardiac fibrosis changes had showed in UUO rats. Immunofluorescence double staining and triple staining showed that infiltrating macrophages could transform into myofibroblasts and secrete extracellular matrix.

   In vitro, aldosterone stimulated macrophages can induce nuclear translocation of the mineralocorticoid receptor(NR3C2). Flow cytometry confirmed that macrophage-to-myofibroblast transition (MMT), and MRB can inhibit this change. In addition, TGF- β or CTGF can also induce MMT.

   The results confirm that long-term UUO can induce cardiorenal syndrome, the MMT is involved in the formation of cardiac fibrosis. Aldosterone activates MR to induce MMT with MR/TGF-β/ CTGF signaling pathway.



〇村田幸久1-3 小林幸司3 坂本直観1 宮崎優介1 掛野仁志1 港高志1.3 岸拓也1.3



病態解明や治療薬の開発を目指す非臨床試験(基礎研究)において、動物モデルの作製とその行動評価は欠かせない。しかし、マウスやラットといった実験動物に、ヒトと同様の表現型が現れているのか?そして、それをどのように評価するべきか? これらの疑問や課題が常に付きまとう。また、薬理・毒性スクリーニングにおける行動評価の効率化や最適化、デジタル化のニーズも非常に高い。これらの疑問や課題の解決するためには、既存の動物行動評価を見直しつつも、新たな評価系の確立を急ぐ必要がある。近年、画像の取得解析技術や人工知能の開発が飛躍的に進み、特に人の行動や情動を解析する様々な技術が開発され、産業応用されつつある。これらの技術は実験動物を含む、動物の行動や情動解析にも応用できる。我々は動物の「心」をどこまで読めるようになったのか?本講演では、我々が進めている画像解析や機械学習を用いた新しい動物行動評価ツールの開発と応用について紹介したい。

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