Tu Zhidan, Shi Yujun, Wang Jinjing, Bao Ji, Bu Hong
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China.
Nephrology (Carlton). 2007 Apr;12(2):166-71. doi: 10.1111/j.1440-1797.2007.00772.x.
To study the expression of connective tissue growth factor (CTGF) in transplanted rat kidney and its relationship with chronic allograft nephropathy (CAN).
Kidney transplantation was performed from Lewis to Fisher 344 allogeneic rat strain, and kidney grafts were harvested at the eighth, 12th and 16th week. The morphological changes were studied, and collagen deposition was determined by Masson trichrome stain. Serum creatinine was examined. The fibrotic process and the CAN grades were evaluated according to Banff 97 schema. The expressions of transforming growth factor beta, CTGF and alpha-smooth muscle actin were detected to assess the development of grafted kidney fibrosis and to discuss their relationships. Spearman correlation was used for correlation study between CTGF expression and development of CAN.
Serum creatinine was promoted in a time-dependent manner. Morphological changes suggested that the grafted kidneys were under abnormalities. At the end stage, focal segmental glomerulosclerosis was seen; tubular epithelial cells lost their phenotype and interstitial fibrosis was notable. Masson trichrome stain showed significant collagen accumulation in a time-dependent manner. Immunohistochemistry and western blotting results showed that the transforming growth factor beta, CTGF and alpha-smooth muscle actin expression were markedly promoted compared with the control group. CTGF was mainly expressed in the plasm of proximal tubular epithelial cells based on the severity of CAN.
Connective tissue growth factor might play an important role in the pathological changes of CAN after kidney transplantation. The expression of CTGF in epithelial cells could act as a molecular marker of interstitial fibrosis and CAN.
研究结缔组织生长因子(CTGF)在大鼠移植肾中的表达及其与慢性移植肾肾病(CAN)的关系。
将Lewis大鼠的肾脏移植到同种异体Fisher 344大鼠体内,于术后第8、12和16周摘取移植肾。观察其形态学变化,采用Masson三色染色法测定胶原沉积情况。检测血清肌酐水平。根据Banff 97标准评估纤维化进程及CAN分级。检测转化生长因子β、CTGF和α-平滑肌肌动蛋白的表达,以评估移植肾纤维化的发展情况并探讨它们之间的关系。采用Spearman相关性分析研究CTGF表达与CAN发展之间的相关性。
血清肌酐呈时间依赖性升高。形态学变化提示移植肾存在异常。终末期可见局灶节段性肾小球硬化;肾小管上皮细胞丧失其表型,间质纤维化明显。Masson三色染色显示胶原沉积呈时间依赖性显著增加。免疫组织化学和蛋白质印迹结果显示,与对照组相比,转化生长因子β、CTGF和α-平滑肌肌动蛋白的表达明显上调。根据CAN的严重程度,CTGF主要表达于近端肾小管上皮细胞的胞质中。
结缔组织生长因子可能在肾移植后CAN的病理变化中起重要作用。CTGF在上皮细胞中的表达可作为间质纤维化和CAN的分子标志物。