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. 2023 Apr;18(2):551-559.
doi: 10.1016/j.jds.2022.08.025. Epub 2022 Sep 17.

Expression of epithelial-mesenchymal transition-associated proteins and proliferating cell nuclear antigen in dihydropyridine-induced gingival overgrowth fibroblasts: A preliminary study

Po-Han Chen  1 , Yaw-Tung Chuang  2 , Chiung-Fang Huang  1   3 , Hsein-Kun Lu  1   2
Affiliations

Expression of epithelial-mesenchymal transition-associated proteins and proliferating cell nuclear antigen in dihydropyridine-induced gingival overgrowth fibroblasts: A preliminary study

Po-Han Chen et al. J Dent Sci. 2023 Apr.

Abstract

Background/purpose: The clinical features of dihydropyridine-induced gingival overgrowth (DIGO), including extracellular matrix accumulation and cell hyperplasia, are regulated by inflammatory factors (e.g., Interleukin-1β [IL-1β]) in combination with calcium channel blockers (e.g., nifedipine [Nif]). We speculated that IL-1β and Nif (IL-1β/Nif) may be the main factor modulating the proliferative potential and turnover of fibroblasts in DIGO.

Materials and methods: We cultured four DIGO fibroblast strains and analysed the possible effects of IL-1β/Nif treatments on epithelial-mesenchymal transition (EMT)-associated proteins. We developed short hairpin ribonucleic acids (shRNAs) and used them to explore the role of IL-1β/Nif in regulating proliferating cell nuclear antigen (PCNA) levels in DIGO tissues.

Results: Our results revealed that compared with control cells, DIGO cells stimulated with IL-1β/Nif had higher levels of the EMT-associated proteins Snail, Slug, and Twist. Moreover, both drugs enhanced androgen receptor (AR), Slug, and PCNA expression.

Conclusion: Taken together, our data indicate that proinflammatory cytokines in combination with calcium channel blockers can regulate the expression of EMT-associated proteins and increase the proliferative potential of DIGO fibroblasts.

Keywords: Dihydropyridine-induced gingival overgrowth; EMT-associated proteins; Interleukin-1β; Nifedipine; PCNA.

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Conflict of interest statement

The authors have no conflicts of interest relevant to this article.

Figures

Figure 1
Figure 1
Western blot used to determine the expression of AR, Snail, and Slug induced by Nif, IL-1β, or both in healthy (control) and DIGO cells. AR (Androgen receptor), DIGO (dihydropyridine-induced gingival overgrowth), IL-1β (interleukin-1β), Nif (nifedipine).
Figure 2
Figure 2
A quantitative real-time polymerase chain reaction was used to determine the messenger ribonucleic acid expression of Twist, Snail, and Slug induced by Nif, IL-1β, or both in healthy (control) and DIGO cells; ∗P < 0.01. GAPDH was used as an internal control for normalisation. DIGO (dihydropyridine-induced gingival overgrowth), IL-1β (interleukin-1β), Nif (nifedipine).
Figure 3
Figure 3
A quantitative real-time polymerase chain reaction was used to determine the messenger ribonucleic acid expression of E-cadherin and N-cadherin induced by Nif, IL-1β, or their combination in healthy (control) and DIGO cells; ∗P < 0.01. GAPDH was used as an internal control for normalisation. DIGO (dihydropyridine-induced gingival overgrowth), E-cadherin (epithelial cadherin), IL-1β (interleukin-1β), N-cadherin (neural cadherin), Nif (nifedipine).
Figure 4
Figure 4
(a) AR levels (b) Slug levels, and (c) PCNA levels were significantly suppressed by AR short hairpin ribonucleic acid plasmid transfection, ∗all P < 0.01. AR (Androgen receptor), IL-1β (interleukin-1β), PCNA (proliferating cell nuclear antigen).
Figure 5
Figure 5
(a) AR levels did not change significantly after Slug short hairpin ribonucleic acid (shRNA) plasmid transfection. (b) Slug levels and (c) PCNA levels were significantly suppressed by Slug shRNA plasmid transfection, ∗both P < 0.01. AR (Androgen receptor), IL-1β (interleukin-1β), PCNA (proliferating cell nuclear antigen).
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