The up‐regulation of type I plasminogen activator inhibitor in human gingival fibroblasts stimulated with cyclosporin A

Abstract

These findings suggest that the up-regulation of PAI-1 may play an important part in the molecular pathogenesis of cyclosporin A-induced gingival overgrowth.

The Upregulation of Transglutaminase‐2 by Cyclosporin A in Human Gingival Fibroblasts Is Augmented by Oxidative Stress

“…CsA is one of the basic immunosuppressants for the prevention of transplant rejection as well as for the management of various autoimmune conditions. CsA was found to contribute to an important change in fibroblast function, and our studies have shown that the upregulation of plasminogen activator inhibitor‐1, 5,6 lysyl oxidase, 7 cystatin C, 8 heat shock protein 47, 9 and hypoxia‐inducible factor‐1α 10 may contribute directly or indirectly to extracellular matrix (ECM) accumulation in CsA‐induced gingival overgrowth. However, the exact mechanism whereby CsA induces gingival overgrowth still remains largely obscure.…”

The modulation of hypoxia-inducible factor-1α/plasminogen activator inhibitor-1 axis in human gingival fibroblasts stimulated with cyclosporine A

“…12 Hypoxia could enhance fibrogenesis via PAI-1 protein involved in ECM modification. As shown in Fig.…”

“…11 Recent results suggest that PAI-1 expression is significantly upregulated in CsA-induced gingival overgrowth specimens. 12 We have found that CsA could upregulate PAI-1 protein expression under hypoxia than normoxia. In addition, PAI-1 protein was markedly abolished by HIF-1a inbitior CAY10585 treatment under hypoxic condition.…”

“…11 Recently, our study has shown that PAI-1 expression is significantly upregulated in CsA-induced gingival overgrowth specimens. 12 To address the mechanisms underlying the hypoxic regulation of PAI-1 expression, the effects of CsA on HGFs were studied in a hypoxia chamber.…”

Upregulation of Slug expression by cyclosporine A contributes to the pathogenesis of gingival overgrowth

“…HGFs were cultured using an explant technique, as described previously. 4,8 Slug expression analysis HGFs were arrested in G 0 by serum deprivation according to our previous experiments. 7 Nearly confluent monolayers of HGFs were washed with a serum-free medium and immediately thereafter exposed, at indicated incubation times, to 0 ng/mL, 100 ng/mL, 200 ng/mL, 500 ng/mL, and 1000 ng/mL CsA (Sigma-Aldrich, St Louis, MO, USA).…”