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  • Title: Induction of matrix metalloproteinase-1 by small interfering RNA targeting connective tissue growth factor in dermal fibroblasts from patients with systemic sclerosis.
    Author: Ishibuchi H, Abe M, Yokoyama Y, Ishikawa O.
    Journal: Exp Dermatol; 2010 Aug; 19(8):e111-6. PubMed ID: 20653770.
    Abstract:
    We aimed to evaluate the effect of small interfering RNA (siRNA) targeting CTGF on extracellular matrices (ECMs) metabolism in normal and SSc fibroblasts. Normal and SSc fibroblasts were transfected with CTGF-specific siRNAs to silence CTGF synthesis. After silencing CTGF, production of type I collagen and matrix metalloproteinase (MMP)-1 by fibroblasts stimulated with TGF-beta was examined. Then quantitative analyses of protein production or mRNA expression of type I collagen, MMP-1,-2,-9 and tissue inhibitor of metalloproteinase (TIMP)-1 with TGF-beta stimulation were carried out. Furthermore, after silencing CTGF, proliferations of normal and SSc fibroblasts were investigated. CTGF-specific siRNA significantly reduced CTGF production. The production of type I collagen was significantly reduced by CTGF silencing in normal fibroblasts. The CTGF silencing significantly increased the production of MMP-1 and decreased the production of TIMP-1 in SSc fibroblasts. The mRNA expression of MMP-1 was increased in CTGF-silenced SSc fibroblasts, but not in normal fibroblasts. There were no significant changes in the production or mRNA expression of other ECM-related genes in normal and SSc fibroblasts. Fibroblast proliferations were suppressed by CTGF silencing in normal and SSc fibroblasts. Our data showed that MMP-1 was increased by CTGF-specific siRNA transfection only in SSc fibroblasts. RNAi targeting CTGF could be a novel therapeutic strategy for SSc.
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