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

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 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.