Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts

Background: It has been proven that the antihypertensive agent nifedipine can cause gingival overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible pathogenetic mech...

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Main Authors: Dorina Lauritano, Giulia Moreo, Fedora Della Vella, Annalisa Palmieri, Francesco Carinci, Massimo Petruzzi
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/11/7/3287
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author Dorina Lauritano
Giulia Moreo
Fedora Della Vella
Annalisa Palmieri
Francesco Carinci
Massimo Petruzzi
author_facet Dorina Lauritano
Giulia Moreo
Fedora Della Vella
Annalisa Palmieri
Francesco Carinci
Massimo Petruzzi
author_sort Dorina Lauritano
collection DOAJ
description Background: It has been proven that the antihypertensive agent nifedipine can cause gingival overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible pathogenetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed significant upregulation in treated cells with respect to the control group, and cell adhesion gene CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time PCR and ELISA. Downregulation was observed for transmembrane receptors ITGA6 and ITGB4, the basement membrane constituent LAMA1 and LAMB1, and the extracellular matrix protease MMP11, MMP16, and MMP26. Conclusions: The obtained data suggested that the pathogenesis of nifedipine-induced gingival overgrowth is characterized by an excessive accumulation of collagen due to the inhibition of collagen intracellular and extracellular degradation pathways.
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spelling doaj.art-0d671726a0b74cc79cffe201ee3dbe162023-11-21T14:24:12ZengMDPI AGApplied Sciences2076-34172021-04-01117328710.3390/app11073287Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human FibroblastsDorina Lauritano0Giulia Moreo1Fedora Della Vella2Annalisa Palmieri3Francesco Carinci4Massimo Petruzzi5Centre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, ItalyCentre of Neuroscience of Milan, Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, ItalyInterdisciplinary Department of Medicine, University of Bari, 70121 Bari, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmoro 8, 40126 Bologna, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyInterdisciplinary Department of Medicine, University of Bari, 70121 Bari, ItalyBackground: It has been proven that the antihypertensive agent nifedipine can cause gingival overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible pathogenetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed significant upregulation in treated cells with respect to the control group, and cell adhesion gene CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time PCR and ELISA. Downregulation was observed for transmembrane receptors ITGA6 and ITGB4, the basement membrane constituent LAMA1 and LAMB1, and the extracellular matrix protease MMP11, MMP16, and MMP26. Conclusions: The obtained data suggested that the pathogenesis of nifedipine-induced gingival overgrowth is characterized by an excessive accumulation of collagen due to the inhibition of collagen intracellular and extracellular degradation pathways.https://www.mdpi.com/2076-3417/11/7/3287drug-induced gingival overgrowthnifedipinehuman gingival fibroblastshypertension therapy side effects
spellingShingle Dorina Lauritano
Giulia Moreo
Fedora Della Vella
Annalisa Palmieri
Francesco Carinci
Massimo Petruzzi
Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
Applied Sciences
drug-induced gingival overgrowth
nifedipine
human gingival fibroblasts
hypertension therapy side effects
title Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
title_full Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
title_fullStr Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
title_full_unstemmed Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
title_short Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts
title_sort biology of drug induced gingival hyperplasia in vitro study of the effect of nifedipine on human fibroblasts
topic drug-induced gingival overgrowth
nifedipine
human gingival fibroblasts
hypertension therapy side effects
url https://www.mdpi.com/2076-3417/11/7/3287
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