Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Rheumatology (Oxford). 2013 May;52(5):790-9. doi: 10.1093/rheumatology/kes379. Epub 2013 Jan 3.
Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation and keratinocyte differentiation. We aimed to investigate the clinical association of serum CTSV levels and the mechanism by which CTSV expression is altered in SSc.
Serum CTSV levels were determined by ELISA in 51 SSc and 18 healthy subjects. CTSV expression was evaluated by immunostaining in SSc and normal skin and by RT-real-time PCR in normal and SSc dermal fibroblasts, normal dermal fibroblasts treated with TGF-β1 or Fli1 siRNA and human dermal microvascular endothelial cells (ECs) treated with Fli1 siRNA.
Serum CTSV levels were significantly lower in dcSSc and lcSSc patients than in healthy controls. In early-stage dcSSc, serum CTSV levels were remarkably and uniformly decreased compared with healthy controls. The decrease in serum CTSV levels in mid- and late-stage dcSSc and in lcSSc was linked to the development of proliferative vasculopathy. CTSV expression was decreased in microvascular ECs, pericytes/vascular smooth muscle cells and keratinocytes of dcSSc and lcSSc skin and in dermal fibroblasts of dcSSc skin compared with control skin. Consistently, CTSV expression was decreased in cultured dermal fibroblasts from early-stage dcSSc. Furthermore, mRNA levels of the CTSV gene were significantly decreased in normal fibroblasts treated with TGF-β1 or Fli1 siRNA and in human dermal microvascular ECs treated with Fli1 siRNA.
Loss of CTSV expression may contribute to the development of fibrosis, vasculopathy and the altered phenotype of keratinocytes in SSc.
组织蛋白酶 V（CTSV）是一种潜在的蛋白水解酶，可调节血管生成过程、胶原降解和角质形成细胞分化。我们旨在研究血清 CTSV 水平与 SSc 中 CTSV 表达改变的机制之间的临床关联。
采用 ELISA 法检测 51 例 SSc 患者和 18 例健康对照者血清 CTSV 水平。采用免疫组化法检测 SSc 及正常皮肤中 CTSV 表达，采用 RT-PCR 法检测正常及 SSc 真皮成纤维细胞、经 TGF-β1 或 Fli1 siRNA 处理的正常真皮成纤维细胞和经 Fli1 siRNA 处理的人真皮微血管内皮细胞（ECs）中 CTSV 表达。
dcSSc 和 lcSSc 患者血清 CTSV 水平明显低于健康对照组。在早期 dcSSc 中，血清 CTSV 水平明显且均匀降低，与健康对照组相比差异有统计学意义。中晚期 dcSSc 和 lcSSc 中血清 CTSV 水平的降低与增生性血管病变的发生有关。dcSSc 和 lcSSc 皮肤中小血管 ECs、周细胞/血管平滑肌细胞和角质形成细胞以及 dcSSc 皮肤真皮成纤维细胞中 CTSV 表达降低。在早期 dcSSc 培养的真皮成纤维细胞中，CTSV 表达也降低。此外，经 TGF-β1 或 Fli1 siRNA 处理的正常成纤维细胞以及经 Fli1 siRNA 处理的人真皮微血管 ECs 中 CTSV 基因的 mRNA 水平显著降低。
CTSV 表达缺失可能导致 SSc 纤维化、血管病变和角质形成细胞表型改变。
