Background/Purpose: Our latest studies have demonstrated that adipocytokines, including adiponectin, apelin, and retinol-binding protein-4, are potentially involved in the development of complicated clinical symptoms associated with systemic sclerosis (SSc). Visfatin is another member of adipocytokines with pro-fibrotic, pro-inflammatory, and immunomodulating properties, having been implicated in the pathogenesis of certain fibrotic and inflammatory autoimmune diseases. As an initial step of a series of studies regarding the role of vistatin in the pathogenesis of SSc, we herein investigated the clinical significance of serum visfatin levels and its contribution to the developmental process in this disorder.

Methods: Serum visfatin levels were determined by a specific ELISA in 57 SSc patients and 19 healthy controls. The effects of visfatin on the mRNA levels of a2(I) collagen (COL1A2) and matrix metalloproteinase-1 (MMP-1) genes were examined in normal and SSc dermal fibroblasts by reverse-transcript real-time PCR. The levels of IL-12p70 produced by THP-1 cells differentiated with IFN-g plus LPS in the presence or absence of visfatin were measured by a specific ELISA.

Results: Serum visfatin levels were comparable among total SSc, diffuse cutaneous SSc, limited cutaneous SSc, and healthy controls. The only finding in a series of analyses regarding the correlation of serum visfatin levels with clinical symptoms and laboratory data was the significantly longer disease duration in dcSSc with elevated serum visfatin levels than in those with normal levels. Consistently, serum visfatin levels were significantly elevated in late stage dcSSc (disease duration of > 6 years), but not in early and mid-stage dcSSc, compared with healthy controls, suggesting the possible contribution of visfatin to the resolution of skin sclerosis in late stage dcSSc. To assess this hypothesis, two sets of in vitro experiments were carried out using dermal fibroblasts and THP-1 cells. Visfatin suppressed the mRNA levels of COL1A2 gene, while increasing the mRNA levels of MMP-1 gene, in a dose-dependent manner in SSc dermal fibroblasts, whereas the mRNA levels of these genes were not affected by visfatin at all in normal dermal fibroblasts, indicating the direct anti-fibrotic effect of visfatin on SSc dermal fibroblasts. Furthermore, visfatin increased the production of IL-12p70 in THP-1 cells differentiated with IFN-g plus LPS in a dose-dependent manner, suggesting the promotion of Th1 immune responses by visfatin.

Conclusion: Visfatin may contribute to the resolution of skin sclerosis in late stage dcSSc via the direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-possible-contribution-of-visfatin-to-the-resolution-of-skin-sclerosis-in-patients-with-diffuse-cutaneous-systemic-sclerosis-via-a-direct-anti-fibrotic-effect-on-dermal-fibroblasts-and-th1-polarizati/