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. 2020 Oct;26(7):1474-1482.
doi: 10.1111/odi.13409. Epub 2020 Jun 3.

Photobiomodulation therapy inhibits oral submucous fibrosis in mice

Min-Hsuan Chiang  1   2 , Kun-Tsung Lee  1   3 , Chia-Hsin Chen  2   4   5   6   7 , Ker-Kong Chen  1   8 , Yan-Hsiung Wang  1   2   7
Affiliations

Photobiomodulation therapy inhibits oral submucous fibrosis in mice

Min-Hsuan Chiang et al. Oral Dis. 2020 Oct.

Abstract

Objectives: Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder. However, the best therapeutic treatment for OSMF remains uncertain. Our previous study showed that photobiomodulation (PBM) therapy and forskolin could reduce arecoline-induced fibrosis reactions via the cAMP pathway. The present study aimed to establish an animal model of areca nut extract (ANE)-induced OSMF and to evaluate the therapeutic potential of PBM and forskolin for ANE-induced OSMF.

Subjects and methods: The mice were divided into five groups. The buccal tissues were harvested for histomorphological analysis and immunoblotting.

Results: Our results showed that PBM significantly reduced the development of ANE-induced OSMF, quantified by changes in submucosal layer thickness and collagen deposition. Additionally, PBM could extensively reduce the protein expression of the fibrotic marker genes alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) in buccal submucous lesions. However, forskolin treatment significantly decreased the protein expression of fibrotic marker genes but slightly decreased the observed histomorphological changes.

Conclusions: We established an ANE-induced OSMF mouse model, which also provided a model for the development of a therapeutic treatment for OSMF. The anti-fibrotic effects of PBM and forskolin may be useful for clinical interventions.

Keywords: alpha-smooth muscle actin; anti-fibrosis; areca nut extract; cAMP; connective tissue growth factor; forskolin.

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Figures

FIGURE 1
FIGURE 1
Histopathological evaluation of the lamina propria and submucosal layer thickness by H&E staining. (a) The injection sites were examined on day 14. The sections were viewed under a microscope at 100× and 400× magnification. Magnified tissue regions are marked by yellow rectangles. (b) The injection sites were examined on day 30. The sections were viewed under a microscope at 100× and 400× magnification. Magnified tissue regions are marked by yellow rectangles. (c) Quantification of the average lamina propria and submucosal layer thickness of the tissue using Image‐Pro software. The results are expressed as the mean ± SD. **p < .01 relative to the PBS control group
FIGURE 2
FIGURE 2
Histopathological evaluation of collagen deposition in the lamina propria layer by Masson's trichrome staining. (a) The buccal injection sites were examined on days 14 and 30. The sections were viewed under a microscope at 100× magnification. (b) The intensity of the blue color representing the collagen density was measured using Image‐Pro software. The results are expressed as the mean ± SD. *p < .05 relative to the PBS control group. ***p < .001 relative to the PBS control group
FIGURE 3
FIGURE 3
Therapeutic effect of PBM and forskolin in ANE‐induced buccal submucous fibrosis. (a) The injection sites were examined by H&E staining on day 30. The sections were viewed under a microscope at 100× magnification. (b) Quantification of the average lamina propria and submucosal layer thickness of the tissue using Image‐Pro software. (c) The buccal injection sites were examined on day 30 by Masson's trichrome staining. The sections were viewed under a microscope at 40× magnification. (d) The intensity of the blue color representing collagen deposition was measured using Image‐Pro software. The results are expressed as the mean ± SD. ***p < .001 compared with the PBS control group, #p < .05 compared with the ANE group, ##p < .01 compared with the ANE group
FIGURE 4
FIGURE 4
PBM and forskolin reduced ANE‐induced fibrotic growth factor expression. (a) The expression levels of the fibrotic markers CTGF and α‐SMA were detected at the indicated time points by immunoblotting. GAPDH was used as a loading control. (b) CTGF and (c) α‐SMA expression were measured using Image‐Pro software. The results are expressed as the mean ± SD. ***p < .001 compared with the PBS control group, #p < .05 compared with the ANE group, ###p < .001 compared with the ANE group
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