Kida Yujiro, Asahina Kinji, Inoue Kouji, Kawada Norifumi, Yoshizato Katsutoshi, Wake Kenjiro, Sato Tetsuji
Department of Anatomy II, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Arch Histol Cytol. 2007 Jul;70(2):95-106. doi: 10.1679/aohc.70.95.
The expression of the cytoglobin/stellate cell activation-associated protein (Cygb/STAP) was recently confirmed in all splanchnic vitamin A-storing cells--including hepatic stellate cells (HSCs)--in normal conditions. In the hepatic fibrous lesion, the expression of Cygb/STAP has been shown to be upregulated in activated HSCs and myofibroblasts (MFs), which have synthesized extracellular matrices. Furthermore, splanchnic vitamin A-storing cells have been reported to be distributed in the kidney. In this study, we clarify the contribution of vitamin A-storing cells to renal fibrosis by focusing on Cygb/ STAP. Adult mice were subjected to unilateral ureteral obstruction (UUO) and kidneys were harvested 1, 3, 7, and 10 days after UUO. Numbers of Cygb/STAP-immunopositive cells as well as Cygb/STAP mRNA 3 days after UUO (UUO day 3 kidney) increased. Vitamin A-autofluorescence was observed in intertubular spaces of controls but gradually declined in a time-dependent manner after UUO. Cygb/STAP+ cells were not completely identical with alpha-smooth muscle actin (alphaSMA)-positive cells in the control or UUO day 7 kidneys. Immunohistochemical analysis for Cygb/STAP and fibulin-2 (Fib), a specific marker for distinguishing MFs from activated HSCs, revealed that the number of Fib+STAP+ cells (MFs) and Fib-STAP+ cells (splanchnic vitamin A-storing cells) significantly increased in UUO day 3 and UUO day 7 kidneys compared with the controls. Our present findings support the concept that Cygb/STAP can be a unique marker for splanchnic fibroblast-like cells, namely the vitamin A-storing cell lineage, and suggest that splanchnic vitamin A-storing cells contribute to renal fibrogenesis in the obstructed kidney.
最近证实，在正常情况下，细胞珠蛋白/星状细胞活化相关蛋白（Cygb/STAP）在所有内脏维生素A储存细胞中均有表达，包括肝星状细胞（HSCs）。在肝纤维化病变中，已表明Cygb/STAP在合成细胞外基质的活化HSCs和成肌纤维细胞（MFs）中表达上调。此外，据报道内脏维生素A储存细胞分布于肾脏。在本研究中，我们通过关注Cygb/STAP来阐明维生素A储存细胞对肾纤维化的作用。成年小鼠接受单侧输尿管梗阻（UUO），并在UUO后1、3、7和10天采集肾脏。UUO后3天（UUO第3天的肾脏）Cygb/STAP免疫阳性细胞数量以及Cygb/STAP mRNA增加。在对照组的肾小管间隙中观察到维生素A自发荧光，但在UUO后呈时间依赖性逐渐下降。在对照组或UUO第7天的肾脏中，Cygb/STAP+细胞与α平滑肌肌动蛋白（αSMA）阳性细胞并不完全相同。对Cygb/STAP和纤连蛋白-2（Fib）进行免疫组织化学分析，Fib是区分MFs与活化HSCs的特异性标志物，结果显示与对照组相比，UUO第3天和UUO第7天的肾脏中Fib+STAP+细胞（MFs）和Fib-STAP+细胞（内脏维生素A储存细胞）数量显著增加。我们目前的研究结果支持以下观点：Cygb/STAP可以作为内脏成纤维细胞样细胞（即维生素A储存细胞系）的独特标志物，并表明内脏维生素A储存细胞在梗阻性肾脏的肾纤维化过程中发挥作用。
