Background/Purpose:

Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation, and keratinocyte differentiation. Although our latest paper demonstrated that cathepsin B, another member of cathepsin family, is potentially involved in the developmental process of dermal fibrosis and vasculopathy in systemic sclerosis (SSc), the role of cathepsin V, to the best of our knowledge, has not been well studies so far in this disorder. Therefore, we herein investigated the clinical correlation of serum CTSV levels and the expression levels of CTSV in skin sections among SSc patients.

Methods:

Serum CTSV levels were determined by enzyme-linked immunosorbent assay in 51 SSc patients and 18 normal controls. The expression levels of CTSV protein in normal and SSc skin were evaluated by immunohistochemistry. The contribution of transcription factor Friend leukemia virus integration 1 (Fli1), whose deficiency is associated with the developmental process of SSc, to the altered expression of CTSV in SSc skin was examined in cultured dermal fibroblasts, dermal microvascular endothelial cells, and keratinocytes by reverse-transcript real-time PCR.

Results:

Serum CTSV levels were significantly lower in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (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 obliterative vasculopathy. In immunohistochemistry, CTSV expression was decreased in microvascular endothelial cells, pericytes/vascular smooth muscle cells, and keratinocytes of dcSSc and lcSSc skin and in dermal fibroblasts of dcSSc skin compared with control skin. Consistently, mRNA levels of CTSV gene were decreased in cultured dermal fibroblasts from early-stage dcSSc and in normal dermal fibroblasts treated with TGF-β1. Furthermore, Fli1 gene silencing by siRNA, which potentially reproduces SSc phenotype in microvascular endothelial cells and keratinocytes, reduced the mRNA levels of CTSV gene in human dermal microvascular endothelial cells and normal human keratinocytes.

Conclusion:

Loss of CTSV expression may contribute to the specific phenotype of fibroblasts, endothelial cells, and keratinocytes in SSc, suggesting the possible involvement of decreased CTSV expression to the developmental process of this disorder.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-possible-contribution-of-decreased-cathepsin-v-expression-to-the-development-of-dermal-fibrosis-proliferative-vasculopathy-and-altered-keratinocyte-phenotype-in-systemic-sclerosis/