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


METHODS
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.


RESULTS
SPARC mRNA levels tended to increase 72 h after CsA treatment, whilst they are undetectable in FK506-treated fibroblasts, compared to VH.


CONCLUSIONS
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.
Gagliano
Nicoletta
N
Department of Human Morphology-LITA, University of Milan, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy. nicoletta.gagliano@unimi.it
Moscheni
Claudia
C
Torri
Carlo
C
Dellavia
Claudia
C
Stabellini
Giordano
G
Ferrario
Virgilio F
VF
Gioia
Magda
M
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*
D015676:Osteonectin; D012333:RNA, Messenger; D016572:Cyclosporine; D016559:Tacrolimus