Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
The Role of Adiponectin in the Pathogenesis of Dermal Fibrosis in Systemic Sclerosis.
Asano, Yoshihide, Masui, Yuri, Kadono, Takafumi, Sato, Shinichi
Adiponectin has been demonstrated to be one of anti-inflammatory and anti-fibrotic factors, suggesting the potential of this cytokine to be involved in the developmental process of systemic sclerosis (SSc). The purpose of this study is to investigate the clinical significance of serum adiponectin levels in patients with SSc and to examine if adiponectin affects the pro-fibrotic phenotype of SSc fibroblasts.
Serum adiponectin levels were determined by enzyme-linked immunosorbent assay in 32 patients with diffuse cutaneous SSc (dcSSc), 28 with limited cutaneous SSc (lcSSc), and 27 healthy controls. No significant difference between these groups existed in terms of sex, age, and body mass index. Normal and SSc fibroblasts were stimulated with adiponectin and mRNA levels of human a2(I) collagen and matrix metalloproteinase 1 genes were determined by real-time PCR. mRNA levels of adiponectin receptor 1 and adiponectin receptor 2 genes in those cells were also evaluated by real-time PCR.
Serum adiponectin levels in dcSSc patients (4.93 ± 6.48 mg/ml) were significantly lower than those in lcSSc patients (9.69 ± 7.61 mg/ml, P < 0.01) and healthy controls (9.36 ± 5.57 mg/ml, P < 0.01). dcSSc patients with disease duration of <= 5 years had significantly decreased serum adiponectin levels (2.15 ± 1.69 mg/ml) than those with disease duration of > 5 years (13.29 ± 8.36 mg/ml, P < 0.01), lcSSc patients with disease duration of <= 5 years (8.07 ± 7.98mg/ml, P < 0.05), lcSSc patients with disease duration of > 5 years (10.9 ± 7.34 mg/ml, P < 0.01), and healthy controls (9.36 ± 5.57 mg/ml, P < 0.01). Longitudinal studies in 5 patients with early dcSSc treated with oral prednisone demonstrated that serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in dcSSc patients. In normal fibroblasts, adiponectin stimulation decreased mRNA levels of human a2(I) collagen gene, while increasing mRNA levels of matrix metalloproteinase 1 gene. In SSc fibroblasts, mRNA levels of adiponectin receptor 1 and adiponectin receptor 2 genes were decreased compared with normal fibroblasts. Consistently, SSc fibroblasts were less sensitive to anti-fibrotic effect of adiponectin than normal fibroblasts.
Serum levels of adiponectin may serve as a useful marker to evaluate the activity of progressive skin sclerosis in dcSSc. As well as the decrease in serum levels of adiponectin, the decreased expression of adiponectin receptors contributes to the establishment of pro-fibrotic phenotype in SSc fibroblasts.
To cite this abstract, please use the following information:
Asano, Yoshihide, Masui, Yuri, Kadono, Takafumi, Sato, Shinichi; The Role of Adiponectin in the Pathogenesis of Dermal Fibrosis in Systemic Sclerosis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2320