Interleukin-33 levels are elevated in chronic allograft dysfunction of kidney transplant recipients and promotes epithelial to mesenchymal transition of human kidney (HK-2) cells.
Interleukin-33 levels are elevated in chronic allograft dysfunction of kidney transplant recipients and promotes epithelial to mesenchymal transition of human kidney (HK-2) cells.
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在肾移植受者的慢性同种异体移植功能障碍中，白细胞介素 33 水平升高，并促进人肾 (HK-2) 细胞上皮细胞向间质细胞的转变。
DOI：
10.1016/j.gene.2017.11.010
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发表时间：
2018-02
期刊：
影响因子：
3.5
通讯作者：
Gu Min
中科院分区：
文献类型：
--
作者：
Xu Zhen;Zhao Chunchun;Wang Zijie;Tao Jun;Han Zhijian;Zhang Wei;Tan Ruoyun;Gu Min
本研究旨在探讨白细胞介素（IL）-33在移植肾间质纤维化中的潜在作用及其相关机制。采用酶联免疫吸附试验（ELISA）检测健康志愿者、稳定肾移植受者（stable kidney transplantation recipients，KTR）（stable）、急性排斥反应（acute rejection，AR）KTR和慢性移植物功能障碍（chronic allograft dysfunction，CAD）KTR患者血清IL-33水平。采用免疫组化（IHC）、Western blotting和实时荧光定量PCR（qRT-PCR）检测正常人和CAD患者肾组织中IL-33的表达。此外，用人IL-33以不同剂量或间隔处理人肾（HK）-2细胞，并使用Western印迹和qRT-PCR通过从这些细胞中提取的蛋白质和mRNA的存在来评估上皮向间质转化（EMT）的标志物。用细胞运动和迁移试验评价细胞运动和迁移。Western blot检测IL-33诱导EMT的机制。最后，采用免疫印迹和免疫组化染色法检测对照组和CAD组肾组织中纤连蛋白、E-cadherin和α-SMA的表达，以及MAPK信号通路的活性水平。CAD组的纤维化程度明显更高。与对照组相比，CAD患者中IL-33显著上调。IL-33在体外可诱导HK-2细胞发生EMT，并呈剂量依赖性和时间依赖性，同时可促进HK-2细胞的运动和迁移能力。此外，p38 MAPK信号通路可能参与IL-33诱导的EMT的发病机制，这与对照组和CAD患者肾脏标本的体内结果一致。IL-33在CAD患者中表达上调，并能促进HK-2细胞的EMT。
This study is aimed to investigate the potential role of interleukin (IL)-33 in transplanted kidney interstitial fibrosis and the associated mechanism. Serum IL-33 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in healthy volunteers, stable kidney transplantation recipients (KTRs) (stable), KTRs with acute rejection (AR), and KTRs with chronic allograft dysfunction (CAD) (CAD). Immunohistochemical (IHC) staining, Western blotting, and quantitative real-time PCR (qRT-PCR) were used to detect the expression of IL-33 in human kidney tissues obtained from control and CAD patients. In addition, human kidney (HK)-2 cells were treated with human IL-33 at different doses or intervals, and the markers of epithelial to mesenchymal transition (EMT) were assessed by the presence of proteins and mRNA extracted from these cells using Western blotting and qRT-PCR. Cell motility and migration were evaluated with a cell motility and migration assay. The mechanism involved in EMT induced by IL-33 was investigated by Western blot. Finally, fibronectin, E-cadherin, and α-SMA expression, as well as the level of activity in the MAPK signaling pathway in the kidney tissues from the control and CAD group were also detected using a Western blot and an IHC staining assay. The intensity of fibrosis was substantially higher in the CAD group. IL-33 was significantly upregulated in the CAD patients compared to the control group. In vitro, IL-33 could induce EMT in a dose-dependent and time-dependent manner and promoted both the cellular motility and migration capabilities of HK-2 cells. Moreover, the p38 MAPK signaling pathway might be involved in the pathogenesis of EMT induced by IL-33, which was consistent with the in vivo results of the kidney specimens from the control and CAD patients. IL-33 was upregulated in CAD patients and could promote EMT of HK-2 cells.
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影响因子：
3.2
作者：
Farris AB;Colvin RB
通讯作者：
Colvin RB
影响因子：
3.8
作者：
Zhu, Jinyu;Carver, Wayne
通讯作者：
Carver, Wayne
影响因子：
6.2
作者：
Nankivell, BJ;Fenton-Lee, CA;Chapman, JR
通讯作者：
Chapman, JR
DOI：
--
发表时间：
2012
期刊：
Clinical transplants
影响因子：
--
作者：
Dong Zhu;M. Everly
通讯作者：
Dong Zhu;M. Everly
DOI：
10.1111/ajt.12696
发表时间：
2014-05
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Maluf DG;Dumur CI;Suh JL;Lee JK;Cathro EP;King AL;Gallon L;Brayman KL;Mas VR
通讯作者：
Mas VR