Study of lysosomal storage disease-intracellular signaling and apoptosis

Farber病是一种罕见的遗传性代谢性疾病，其主要症状是由于溶酶体酸性神经酰胺酶缺乏而导致皮下结节富含神经酰胺。为了阐明神经酰胺在细胞信号转导机制中的作用，我检测了细胞通透性神经酰胺诱导的结节和巨噬细胞样细胞系中的表达基因。根据这些结果，我推测神经酰胺的堆积通过上调巨噬细胞趋化蛋白1(MCP-1)基因的表达而诱导巨噬细胞在结节内的浸润，并诱导转化生长因子-β基因的表达。这些结果部分解释了结节形成和巨噬细胞浸润的发病机制。

Farber disease is a rare inherited metaboric disorder, in which cardinal symptom is ceramide enriched subcutaneous nodules due to a deficiency of lysosomal acid ceramidase. I examined expressed genes in nodules from a patient and macrophage like cell lines induced by cell permeable ceramide, to elucidate the roll of ceramide in cell signaling mechanism. From these results, I deduced that ceramide accumulation induced macrophage infiltration in nodules through the up-regulation of the MCP-1 (macrophage chemoattractant protein 1) gene expression and also induced TGF-β gene expression. These results partly explain the pathogenesis of nodule formation and macrophage infiltration.