SHIUAN-SHINN LEEFU-MEI HUANGCHENG-CHIA YUSHUN-FA YANGYU-CHAO CHANG2026-10-162026-10-162015-01-01Pure ID: 15124430Pure UUID: 1b3bf3fd-1e8a-4b77-992b-f32ad69d8a2e10.1016/j.jfma.2012.08.018https://www.scopus.com/pages/publications/84921437898https://scholars.csmu.edu.tw/handle/123456789/34149Background/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.6enjournal article