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Calycosin pretreatment enhanced the therapeutic efficacy of mesenchymal stem cells to alleviate unilateral ureteral obstruction-induced renal fibrosis by inhibiting necroptosis

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机构： [1]Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand [2]Research Center of Integrated Traditional Chinese and Western Medicine, Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Sichuan, China [3]Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand [4]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Sichuan, China

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Bone marrow-derived mesenchymal stem cells (MSCs) show antifibrotic activity in various chronic kidney diseases. Here, we aimed to investigate whether Calycosin (CA), a phytoestrogen, could enhance the antifibrotic activity of MSCs in primary tubular epithelial cells (PTECs) induced by TGF-β1 and in a mouse model of unilateral ureteral obstruction (UUO). We found that MSCs treatment significantly inhibited fibrosis, and CA pretreatment enhanced the effects of MSCs on fibrosis in vitro. Consistent with the in vitro studies, MSCs alleviated tubular injury and renal fibrosis in mice after UUO, and CA-pretreated MSCs resulted in more significant improvements in tubular injury and renal fibrosis than MSCs after UUO. Moreover, MSCs treatment significantly inhibited necroptosis by repressing the elevation of MLKL, RIPK1, and RIPK3 in PTECs treated by TGF-β1and in mice after UUO, and CA-pretreated MSCs were superior to MSCs in alleviating necroptosis. MSCs significantly reduced TNF-α and TNFR1 expression induced by TGF-β1 in PTECs and inhibited TGF-β1, TNF-α, and TNFR1 expression induced by UUO in mice. These effects of MSCs were significantly enhanced after CA pretreatment. Therefore, our results suggest that CA pretreatment enhances the antifibrotic activity of MSCs by inhibiting TGF-β1/TNF-α/TNFR1 signaling-induced necroptosis.Copyright © 2022 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 3 区药学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区药学

第一作者：

第一作者机构： [1]Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand [2]Research Center of Integrated Traditional Chinese and Western Medicine, Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Sichuan, China [4]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Sichuan, China

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通讯机构： [1]Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand [2]Research Center of Integrated Traditional Chinese and Western Medicine, Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Sichuan, China [4]Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Sichuan, China [*1]Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No.182 Chunhui Road, Longmatan District, 646000, Sichuan, China. [*2]Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, 239 Huay Kaew Road, Suthep, Muang, Chiang Mai, 50200, Thailand

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