Differential effect of Cyclosporin A and FK506 on SPARC mRNA expression by human gingival fibroblasts

Department of Human Morphology-LITA, University of Milan, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy.
Biomedecine [?] Pharmacotherapy (Impact Factor: 2.02). 07/2005; 59(5):249-52. DOI: 10.1016/j.biopha.2004.06.005
Source: PubMed


Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein that mediates cell-matrix interactions. In adults, its expression is mostly limited to tissue undergoing remodeling. During the development of Cyclosporin A (CsA)-induced gingival overgrowth (GO) a remodeling of the connective compartment occurs. By contrast, clinical trials showed that FK506 is not related to GO. SPARC expression and its involvement in GO is unknown. Our aim was, therefore, to analyze the effect of CsA and FK506 on SPARC gene expression.
Cultured human gingival fibroblasts were incubated with CsA, FK506 or with their vehicle (VH) for 24, 48 and 72 h. SPARC gene expression was determined by RT-PCR.
SPARC mRNA levels tended to increase 72 h after CsA treatment, whilst they are undetectable in FK506-treated fibroblasts, compared to VH.
This gene expression profile is consistent with the involvement of SPARC in the mechanisms leading to the development of CsA-induced GO. By contrast, the undetectable SPARC mRNA levels in FK506-treated fibroblasts suggest that FK506 may be associated with a role of ECM stabilization, that does not induce GO.

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    • "In adults, the expression of SPARC is limited mostly to tissue undergoing morphogenesis or remodeling due to wound healing, disease, or natural processes (Masson et al., 1998; Brekken and Sage, 2001; Gagliano et al., 2005). SPARC is expressed at high levels in bone tissue but is widely distributed in many other tissues, such as connective tissues, including the soft and mineralized tissue of teeth and their supporting periodontal tissues, according to the high turnover of the remodeling of healthy oral connective tissue (Bartold et al., 2000; Sodek et al., 2002). "
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    • "In agreement with previous studies (Hernandez et al, 2000; James et al, 2000), the results of the present investigation show that tacrolimus administration for brief periods of treatment (60 and 120 days) does not induce gingival overgrowth. It has been suggested that in vitro tacrolimus does not affect the collagen type I gene and protein expression, transforming growth factor (TGF-b1) and tissue inhibitor of matrix metalloproteinase (MMPs) (TIMP-1) mRNA levels, although it significantly increases MMP-1 gene and protein expression and MMP-2 mRNA levels (Gagliano et al, 2005b). "
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