Miyamoto Yohei, Myomoto Akira, Sakaguchi Yuka, Yamaguchi-Yamada Misuzu, Uchio-Yamda Kozue, Manabe Noboru
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc, Tebiro, Kamakura, Kanagawa, Japan.
Exp Anim. 2009 Jul;58(4):375-82. doi: 10.1538/expanim.58.375.
ICR-derived glomerulonephritis (ICGN) mice are a known inbred strain with hereditary nephrotic syndrome and are considered a good animal model of human idiopathic nephrotic syndrome. ICGN mice show proteinuria at a young age, and hypoalbuminemia, hyperlipidemia, anemia and edema accompanies their symptoms with aging. In addition, ICGN mice develop severe anemia with the progression of renal fibrosis similar to human chronic kidney disease (CKD). Recently, tissue transglutaminase (tTG) has been shown to be related to the renal fibrosis in several animal models and CKD patients. In the present study, we investigated the relationship between the progression of renal fibrosis and the localization of tTG in the kidneys using histochemistry and image analysis. Male ICGN mice aged 26-43 weeks were used. They were divided into two groups of early and terminal stages of renal fibrosis, based on plasma levels of blood urea nitrogen (BUN). Normal ICR males aged 11 weeks were used as a control group. tTG was localized to the interstitium in the normal ICR mice. In the early stage of renal fibrosis, the localization of tTG increased in renal tubules showing luminal dilation, as well as in the interstitium; however, the amount of tubular and interstitial tTG decreased in the late stage. In the glomeruli, tTG-immunoreactivity decreased in the late stage of renal fibrosis, despite the progression of glomerular sclerosis. The results suggest that epsilon(gamma-glutamyl) lysine cross-linking is not directly related to the progression of renal fibrosis in ICGN mice.
ICR衍生的肾小球肾炎（ICGN）小鼠是一种已知的具有遗传性肾病综合征的近交系，被认为是人类特发性肾病综合征的良好动物模型。ICGN小鼠在年轻时就出现蛋白尿，随着年龄增长，低白蛋白血症、高脂血症、贫血和水肿伴随其症状出现。此外，ICGN小鼠随着肾纤维化的进展会出现严重贫血，类似于人类慢性肾脏病（CKD）。最近，组织转谷氨酰胺酶（tTG）已被证明在几种动物模型和CKD患者中与肾纤维化有关。在本研究中，我们使用组织化学和图像分析研究了肾纤维化进展与tTG在肾脏中的定位之间的关系。使用26至43周龄的雄性ICGN小鼠。根据血浆尿素氮（BUN）水平，将它们分为肾纤维化早期和晚期两组。使用11周龄的正常ICR雄性小鼠作为对照组。在正常ICR小鼠中，tTG定位于间质。在肾纤维化早期，tTG的定位在显示管腔扩张的肾小管以及间质中增加；然而，在晚期，肾小管和间质中的tTG量减少。在肾小球中，尽管肾小球硬化进展，但在肾纤维化晚期tTG免疫反应性降低。结果表明，ε（γ-谷氨酰）赖氨酸交联与ICGN小鼠肾纤维化的进展没有直接关系。
