Characterization of a Novel Dermal Fibrosis Model Induced by Areca Nut Extract that Mimics Oral Submucous Fibrosis

Abstract

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder and areca quid chewing is the main etiological factor. However, the molecular mechanism underlying OSF remains unclear, partly due to the lack of an appropriate animal model. The present study aimed to establish and characterize an animal model of areca nut extract (ANE)-induced skin fibrosis that mimics OSF. Mice were divided into 4 groups: the control group; the bleomycin group; and the ANE10 and ANE20 groups, which received 10mg/ml and 20mg/ml subcutaneous (SC) injection of ANE, respectively. Skin fibrosis was evaluated by histological analyses. Additionally, the expression levels of the fibrotic marker genes were determined by immunohistochemical staining and immunoblotting. ANE administration significantly increased dermal thickness and collagen deposition compared with the control group. Moreover, ANE induced the expression of the fibrotic marker genes alpha smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) in the skin lesions. The SC injection of ANE successfully induced skin fibrosis, exhibiting characteristics similar to those of OSF. This model may facilitate future studies of the mechanism underlying OSF.

Photobiomodulation therapy inhibits oral submucous fibrosis in mice

“…In our previous study, we showed that subcutaneous injection of ANE can induce dermal fibrosis within one month (Chiang et al, 2016). In this study, we found that injection of ANE into buccal tissues also induced fibrosis within one month, and pathological features similar to those of OSMF were observed.…”

“…We modified our previous ANE-induced dermal fibrosis model to investigate whether oral submucosal injection of ANE could induce OSMF (Chiang et al, 2016). Mice were treated with ANE, and the morphologic changes were analyzed on days 14 and 30 (Figure 1a, b).…”

“…Recently, we successfully established a mouse model of localized dermal fibrosis that mimics the pathologic development of OSMF within 4 weeks after subcutaneous injection of ANE in the backs of the mice (Chiang et al, 2016). In addition, our previous study found that photobiomodulation (PBM) and forskolin could reduce arecoline-induced fibrosis via the cAMP pathway (Yeh et al, 2017).…”

Multifaceted Mechanisms of Areca Nuts in Oral Carcinogenesis: the Molecular Pathology from Precancerous Condition to Malignant Transformation

“…In the past few decades, accumulated studies have demonstrated that areca nuts can induce premalignant and malignant transformation of oral tissues. In animal model studies, areca nut extract (or the ingredient cocktail) can be an effective tumor initiator or promoter and can induce premalignant oral lesions, including submucosal fibrosis 9, 10 and squamous hyperplasia 11-13, or result in malignant transformation 13-16. For example, arecaidine displays a synergistic effect in the 7,12-dimethyl-benz(a)anthracene (DMBA)- induced tumor formation in the cheek pouch of hamster 15.…”

LINC00312/YBX1 Axis Regulates Myofibroblast Activities in Oral Submucous Fibrosis

“…Currently, there was no well-established animal model to mimic the pathogenesis of OSF. These methods were either time consuming [29] or not suitable for studying fibrosis in the oral mucosae as the induced fibrosis occurred in the back [30]. Further studies are needed to examine the effect of targeting YBX1 on relief OSF symptoms in vivo.…”