Cyclosporin‐A increases type I procollagen production and mRNA level in human gingival fibroblasts in vitro

Abstract

In order to study the pathogenesis of gingival overgrowth induced by the immunosuppressive drug cyclosporine-A (CyA), we investigated its effect on 3H thymidine incorporation and on collagen production and mRNA levels in fibroblast cultures obtained from normal human gingiva. At concentrations of 100, 500 and 1000 ng/ml, CyA did not modify thymidine incorporation after 24 and 72 h of incubation. However, after 24 h it significantly increased the level of 3H proline-containing proteins in the medium. In addition, CyA increased alpha-procollagen chains by up to three times. This CyA-induced change was related to a rise in the level of type I procollagen. The CyA effect on fibroblasts was markedly reduced by cycloheximide, an inhibitor of protein synthesis, and it correlated well with an increase of type I procollagen mRNA. Overall, our data indicate a direct stimulatory action of CyA on collagen synthesis, but not on DNA synthesis, in human gingival fibroblasts.

Involvement of apoptotic signals in cyclosporin A-induced proliferation of human gingival fibroblast

“…Furthermore, these effects of CsA on human fibroblast proliferation may vary according to individual cell strains 9) . In contrast, other previous studies have suggested that CsA increases production of extracellular matrix, collagen and interleukin-6 but simultaneously decreases proliferation of human gingival fibroblast 10,11) . Nevertheless, it is apparent that CsA increases cell proliferation of human gingival fibroblast in vitro 12) .…”

Proteomic Analysis in Cyclosporin A-Induced Overgrowth of Human Gingival Fibroblasts

“…13,14) In contrast, other reports showed that CsA has no effect on proliferation or an inhibitory effect in gingival fibroblasts. 16,23) Nevertheless, the present study showed that CsA promoted the proliferation of HGF over 0.1-10 mM in a dose-and time-dependent manner (Fig. 1).…”

Cyclosporin A-induced gingival overgrowth is not associated with myofibroblast transdifferentiation

“…Many studies have shown increased transcriptional and translational levels of type I collagen in both tissue and fibroblast cultures derived from CyA-induced gingival overgrowth. [20][21][22] A growing body of evidence has connected myofibroblasts with the pathogenesis of several fibrotic processes, since they are the main source of the increased extracellular matrix deposition. 7,8,23,24 The regulatory cytokine TGF-β1 has been traditionally considered an inducer of the myofibroblast phenotypes both in vivo and in vitro.…”