Human mesenchymal stromal cells ameliorate cisplatin-induced acute and chronic kidney injury via TSG-6

作者全名："Tang, Ming; Shen, Linguo; Tang, Maozhi; Liu, Ling; Rao, Zhengsheng; Wang, Zhilin; Wang, Yadi; Yin, Supei; Li, Shujing; Xu, Guilian; Zhang, Keqin"

作者地址："[Tang, Ming; Shen, Linguo; Tang, Maozhi; Liu, Ling; Rao, Zhengsheng; Wang, Zhilin; Wang, Yadi; Yin, Supei; Li, Shujing; Zhang, Keqin] Chongqing Med Univ, Affiliated Hosp 2, Urinary Nephropathy Ctr, Chongqing 400065, Peoples R China; [Xu, Guilian] Third Mil Med Univ, Dept Immunol, Army Med Univ, Chongqing 400038, Peoples R China"

通信作者："Xu, GL (通讯作者)，30 Gaotanyan Main St, Chongqing 400038, Peoples R China.; Zhang, KQ (通讯作者)，288 Tianwen Ave, Chongqing, Peoples R China."

来源：STEM CELLS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001293845900001

JCR分区：Q1

影响因子：5.2

年份：2024

卷号：42

期号：9

开始页：848

结束页：859

文献类型：Article

关键词：mesenchymal stromal cells; TSG-6; cisplatin; kidney injury

摘要："Cisplatin is widely used in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor-alpha-stimulated gene/protein 6 (rhTSG-6), or PBS through the tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. Human BM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen, tubular injury, collagen deposition, alpha-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in the serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, the knockdown of the TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviates cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion. Graphical Abstract"

基金机构：National Natural Science Foundation of China [82300855]; China Postdoctoral Science Foundation [2021M700634]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0240]; Chongqing Postdoctoral Science Special Foundation [2021XM3088]

基金资助正文："This work was supported by the National Natural Science Foundation of China (NO. 82300855), China Postdoctoral Science Foundation (2021M700634), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0240) and Chongqing Postdoctoral Science Special Foundation (2021XM3088)."