Long non-coding RNAs (lncRNAs) are thought to have various functions other than RNA silencing. We tried to evaluate the expression of lncRNAs in patients with systemic sclerosis (SSc) and determined whether lncRNAs controls collagen expression in dermal fibroblasts. lncRNA expression was determined by real-time PCR and in situ hybridization. Protein and mRNA levels of collagen were analysed using immunoblotting and real-time PCR. We found TSIX, one of the lncRNAs, was overexpressed in SSc dermal fibroblasts both in vivo and in vitro, which was inhibited by the transfection of transforming growth factor (TGF)-β1 siRNA. TSIX siRNA reduced the mRNA expression of type I collagen in normal and SSc dermal fibroblasts, but not the levels of major disease-related cytokines. In addition, TSIX siRNA significantly reduced type I collagen mRNA stability, but not protein half-lives. Furthermore, we first investigated serum lncRNA levels in patients with SSc, and serum TSIX levels were significantly increased in SSc patients. TSIX is a new regulator of collagen expression which stabilizes the collagen mRNA. The upregulation of TSIX seen in SSc fibroblasts may result from activated endogenous TGF-β signalling and may play a role in the constitutive upregulation of collagen in these cells. Further studies on the regulatory mechanism of tissue fibrosis by lncRNAs in SSc skin lead to a better understanding of the pathogenesis, new diagnostic methods by their serum levels and new therapeutic approaches using siRNAs.

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Tenascins are a family of large multimetric extracellular matrix (ECM) proteins. Among them, large molecular weight variant tenascin-C is known to be specifically expressed in pathological conditions. However, no link between tenascin-C and collagen diseases has been established. The aim of our study was to determine the serum tenascin-C levels in patients with various collagen diseases, and to evaluate the possibility that serum levels of tenascin-C can be a useful marker for collagen diseases, correlating with the pathogenesis. Serum tenascin-C levels of 33 patients with scleroderma (SSc), 10 patients with scleroderma spectrum disorder (SSD), 15 patients with localized scleroderma (LSc), 12 patients with dermatomyositis (DM), 10 patients with systemic lupus erythematosus (SLE) and 15 healthy controls were measured with specific enzyme-linked immunosorbent assays. Serum tenascin-C levels were significantly elevated in patients with SSc, SSD and LSc than in healthy controls. Significantly higher total skin thickness score or higher incidence of pitting scars/ulcers and diffuse pigmentation were observed in SSc patients with elevated tenascin-C levels than in those with normal levels. Our study suggests that serum tenascin-C levels are increased in fibrotic conditions, and that tenascin-C contributes to the pathogenesis of vascular damage as well as fibrosis in SSc patients. Clarifying the role of tenascin-C in the pathogenesis of collagen diseases may lead to a new therapeutic approach.

Expression of microRNA (miRNA) in the skin in dermatomyositis has not previously been studied in detail. In this study, we performed miRNA array analysis using miRNAs purified from dermatomyositis-involved skin and normal skin, and found that several miRNAs were up- or down-regulated in dermatomyositis skin. Among them, we focused on miR-7, one of the most down-regulated miRNAs in dermatomyositis skin. Total miRNAs were purified from serum, and hsa-miR-7 levels were measured with quantitative real-time PCR using the specific primer. Serum levels of miR-7 were significantly decreased in patients with dermatomyositis compared with normal subjects or patients with other autoimmune diseases. Thus, serum miR-7 levels might be a possible diagnostic marker for dermatomyositis. Clarifying the up- or down-stream events of down-regulated miR-7 in patients with dermatomyositis may lead to further understanding of the disease and a new therapeutic approach.