Division of Gastroenterology and Hepatology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
Digestion. 2011;84(2):156-67. doi: 10.1159/000327380. Epub 2011 May 12.
BACKGROUND/AIMS: The non-lysosomal glucosylceramidase, β-glucosidase (Gba2), hydrolyzes glucosylceramide to glucose and ceramide (Cer). Cer is a potent second-messenger lipid that plays an important role in signaling cascades involved in apoptosis. The aim of this study was to investigate whether Gba2 knock-out (Gba2(-/-)) affects the extent of dextran sulfate sodium (DSS)-induced colitis in mice.
Acute colitis was induced in wild-type (WT) and Gba2(-/-) mice by administration of 2% DSS in drinking water. After 7 days, mice underwent colonoscopy and were sacrificed.
Both DSS-treated WT (n = 10) and Gba2(-/-) (n = 12) mice showed elevated histological and endoscopic scores compared to respective H(2)O controls (n = 9 each). However, no significant differences between the DSS groups were detected. Flow cytometric analysis of propidium iodide staining, cleavage of caspases-3 and -8, indicative for apoptosis, as well as Cer levels were not altered in DSS-treated WT or Gba2(-/-) mice. Gba2(-/-) resulted in slightly decreased expression of glucocerebrosidase (Gba1) as well as in upregulation of proteins being involved in cellular regeneration, such as STAT3 (signal transducer and activator of transcription), JNK and iNOS, upon DSS treatment.
We demonstrate that Gba2(-/-) does not affect the extent of DSS-induced inflammation in mice, however, it might be involved in tissue regeneration in response to toxic agents.
背景/目的：非溶酶体葡萄糖神经酰胺酶，β-葡萄糖苷酶（Gba2），将葡萄糖神经酰胺水解为葡萄糖和神经酰胺（Cer）。Cer 是一种有效的第二信使脂质，在涉及细胞凋亡的信号级联反应中发挥重要作用。本研究旨在探讨 Gba2 敲除（Gba2(-/-)）是否会影响葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的严重程度。
通过在饮用水中添加 2% DSS 来诱导野生型（WT）和 Gba2(-/-) 小鼠的急性结肠炎。7 天后，对小鼠进行结肠镜检查并进行安乐死。
与各自的 H2O 对照组（每组 n = 9）相比，DSS 处理的 WT（n = 10）和 Gba2(-/-)（n = 12）小鼠的组织学和内镜评分均升高。然而，DSS 组之间未检测到显著差异。碘化丙啶染色、caspase-3 和 -8 切割（提示细胞凋亡）以及 Cer 水平的流式细胞术分析在 DSS 处理的 WT 或 Gba2(-/-) 小鼠中均未改变。Gba2(-/-)导致 DSS 处理时葡萄糖脑苷脂酶（Gba1）的表达略有降低，并且涉及细胞再生的蛋白质如 STAT3（信号转导和转录激活因子）、JNK 和 iNOS 的表达上调。
我们证明 Gba2(-/-) 不会影响 DSS 诱导的小鼠炎症的严重程度，但它可能参与对有毒物质的组织再生。
