Upregulation of transforming growth factor-beta1 and vascular endothelial growth factor gene and protein expression in cyclosporin-induced overgrown edentulous gingiva in rats.
BACKGROUND
To examine the effects of cyclosporin A (CsA) on the expression of growth factors in induced gingival overgrowth with limited contributing factors arising from local inflammation caused by bacterial plaque, this study of gingival overgrowth was designed on the edentulous ridge of rats.


METHODS
After a 3-week healing period following maxillary molar extractions, 16 five-week-old male Sprague-Dawley rats were assigned to CsA and control groups. Animals in the CsA group were fed 30 mg/kg CsA daily, whereas the control rats received a mineral oil vehicle instead. After 4 weeks, all animals were sacrificed, and the morphology of edentulous ridges was recorded by dental impression. The gingivae on the left-hand side were dissected and stored for mRNA analysis, whereas the gingivae on the right-hand side were fixed in 4% paraformaldehyde for immunohistochemistry (IHC) analysis of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor beta (PDGF-beta), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF).


RESULTS
The edentulous gingivae were enlarged and the body weights were reduced in the CsA-treated animals compared to controls. The mRNA expressions of TGF-beta1, IGF-1, and VEGF were higher in the gingivae of the CsA group than in the control group. In addition, a greater mRNA expression (7.21-fold) of VEGF was demonstrated in the CsA group than in the control group by real-time polymerase chain reaction (PCR). The percentages of cells staining positive for TGF-beta1 and VEGF were significantly greater in the CsA rats than in the control rats.


CONCLUSIONS
Greater mRNA expression and positive staining for TGF-beta1 and VEGF were observed in the edentulous gingivae of rats that received CsA. Therefore, CsA may upregulate TGF-beta1 and VEGF gene expression and protein secretion in CsA-induced gingival overgrowth.
Chen
Yen-Teen
YT
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Tu
Hsiao-Pei
HP
Chin
Yu-Tang
YT
Shen
E-Chin
EC
Chiang
Cheng-Yang
CY
Gau
Ching-Hwa
CH
Fu
Earl
E
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D008297:Male; D009066:Mouth, Edentulous / Q000473:pathology*; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000187:drug effects*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D016572:Cyclosporine