Zhao Shi-Qi, Xue Zhen-Zhen, Wang Ling-Zhang
Emergency Intensive Care Unit, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Exp Ther Med. 2017 Dec;14(6):6138-6146. doi: 10.3892/etm.2017.5319. Epub 2017 Oct 17.
The present study aimed to investigate the association between high mobility group protein B1 (HMGB1), transforming growth factor-β1 (TGF-β1), nuclear factor-κB (NF-κB) and chronic allograft nephropathy (CAN) and to identify the clinical significance of HMGB1, TGF-β1, NF-κB on patients with CAN. Between September 2012 and November 2014, 27 patients with CAN diagnosed by biopsy were enrolled in the present study and a further 30 patients that underwent nephrectomy following trauma were selected as the control group. Immunohistochemical staining with HMGB1, TGF-β1 and NF-κB expression in the renal tissues, and western blot analysis were used to measure the relative expression of HMGB1, TGF-β1 and NF-κB. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to estimate the relative expression of HMGB1, TGF-β1 and NF-κB mRNA. Statistical analysis was used to calculate the association between HMGB1, TGF-β1 and NF-κB expression and CAN grade. Immunohistochemical staining demonstrated that HMGB1, TGF-β1 and NF-κB had markedly positive expression rates in renal tubular epithelial cell cytoplasm and membranes in CAN renal tissues, and the positive rates of HMGB1, TGF-β1 and NF-κB increased with the aggravation of CAN pathological grade (I, II and III). The results of western blot analysis indicated that the expression levels of HMGB1, TGF-β1 and NF-κB were significantly higher in the CAN group, compared with the normal group (P<0.05), and the expression levels increased with the progression of CAN grade. A positive association among HMGB1, TGF-β1 and NF-κB expression was identified. RT-qPCR analysis demonstrated that the expression of HMGB1, TGF-β1 and NF-κB mRNA in the CAN group was significantly higher than in the normal group (P<0.05), and the relative expression level of HMGB1, TGF-β1 and NF-κB mRNA not only increased with the aggravation of CAN grade, but was also positively associated with the expression of HMGB1, TGF-β1 and NF-κB, respectively. The abnormal expression of HMGB1, TGF-β1 and NF-κB is therefore, an important manifestation of CAN and the expression of HMGB1, TGF-β1 and NF-κB mRNA in the renal tissues are significantly associated with CAN pathological progression. HMGB1, TGF-β1 and NF-κB may form a signaling pathway that leads to the occurrence of CAN, which induces renal interstitial fibrosis.
本研究旨在探讨高迁移率族蛋白B1（HMGB1）、转化生长因子-β1（TGF-β1）、核因子-κB（NF-κB）与慢性移植肾肾病（CAN）之间的关联，并确定HMGB1、TGF-β1、NF-κB对CAN患者的临床意义。2012年9月至2014年11月，本研究纳入了27例经活检确诊为CAN的患者，并选取另外30例创伤后接受肾切除术的患者作为对照组。采用免疫组织化学染色检测肾组织中HMGB1、TGF-β1和NF-κB的表达，并通过蛋白质印迹分析来测定HMGB1、TGF-β1和NF-κB的相对表达。采用逆转录定量聚合酶链反应（RT-qPCR）来评估HMGB1、TGF-β1和NF-κB mRNA的相对表达。运用统计学分析来计算HMGB1、TGF-β1和NF-κB表达与CAN分级之间的关联。免疫组织化学染色显示，在CAN肾组织的肾小管上皮细胞胞质和细胞膜中，HMGB1、TGF-β1和NF-κB有明显的阳性表达率，且HMGB1、TGF-β1和NF-κB的阳性率随着CAN病理分级（I、II和III级）的加重而升高。蛋白质印迹分析结果表明，与正常组相比，CAN组中HMGB1、TGF-β1和NF-κB的表达水平显著更高（P<0.05），且表达水平随着CAN分级的进展而升高。HMGB1、TGF-β1和NF-κB表达之间存在正相关。RT-qPCR分析表明，CAN组中HMGB1、TGF-β1和NF-κB mRNA的表达显著高于正常组（P<0.05），且HMGB1、TGF-β1和NF-κB mRNA的相对表达水平不仅随着CAN分级的加重而升高，还分别与HMGBI、TGF-β1和NF-κB的表达呈正相关。因此，HMGB1、TGF-β1和NF-κB的异常表达是CAN的重要表现，肾组织中HMGB1、TGF-β1和NF-κB mRNA的表达与CAN病理进展显著相关。HMGB1、TGF-β1和NF-κB可能形成一条导致CAN发生的信号通路，进而诱导肾间质纤维化。
