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

doi:10.1016/j.jfma.2012.08.018

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 期刊論文 > Item 310902500/15697

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/15697

Title:	The modulation of hypoxia-inducible factor-1α/plasminogen activator inhibitor-1 axis in human gingival fibroblasts stimulated with cyclosporine A.
Authors:	CH, Tsai;SS, Lee;FM, Huang;CC, Yu;SF, Yang;YC, Chang
Contributors:	中山醫大口腔科學研究所
Keywords:	cyclosporine A;gingival fibroblasts;gingival overgrowth;hypoxia-inducible factor-1α;plasminogen activator inhibitor-1
Date:	2015-01
Issue Date:	2016-08-09T08:26:46Z (UTC)
ISSN:	0929-6646
Abstract:	BACKGROUND/PURPOSE: The prominent side effect of the immunosuppressive drug cyclosporine A (CsA) is gingival overgrowth. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal gingival tissues and CsA-induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of HIF-1α expression. METHODS: Fifteen CsA-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of CsA on the expression of HIF-1α in cultured human gingival fibroblasts. The effects of CsA on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia. RESULTS: HIF-1α staining in gingival tissue was stronger in CsA-induced gingival overgrowth group than normal gingival group (p < 0.05). The expression of HIF-1α was significantly higher in CsA-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p = 0.041). CsA was found to upregulate HIF-1α protein in a dose-dependent manner (p < 0.05). Hypoxia increased CsA-induced PAI-1 protein expression than normoxic conditions (p < 0.05). CONCLUSION: These results suggest that HIF-1α expression is significantly upregulated in CsA-induced gingival overgrowth specimens. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in gingival tissues. Copyright © 2012. Published by Elsevier B.V.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/15697 http://dx.doi.org/10.1016/j.jfma.2012.08.018
Relation:	Journal of the Formosan Medical Association Volume 114, Issue 1, January 2015, Pages 58–63
Appears in Collections:	[牙醫學系暨碩士班] 期刊論文

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