West China Journal of Stomatology ›› 2025, Vol. 43 ›› Issue (6): 829-836.doi: 10.7518/hxkq.2025.2025182

• Basic Research • Previous Articles    

Cannabinoid receptor 2 inhibition on acantholysis in oral mucosal pemphigus

Liu Huijuan1, Song Peng2, Hou Yali2, Huo Xiao3, Mi Lijin4, Liu Chunyan5()   

  1. 1.Key Laboratory of Stomatology, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Hebei Technology Innovation Center of Oral Health, Shijiazhuang 050017, China
    2.Dept. of Pathology, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomato-logy, Hebei Technology Innovation Center of Oral Health, Shijiazhuang 050017, China
    3.Dept. of Oral Medicine, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Hebei Technology Innovation Center of Oral Health, Shijiazhuang 050017, China
    4.Dept. of Clinical Laboratory, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Hebei Technology Innovation Center of Oral Health, Shijiazhuang 050017, China
    5.Dept. of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Hebei Technology Innovation Center of Oral Health, Shijiazhuang 050017, China
  • Received:2025-04-24 Revised:2025-07-14 Online:2025-12-01 Published:2025-11-27
  • Contact: Liu Chunyan E-mail:chunyanliu@hebmu.edu.cn
  • Supported by:
    Medical Science Research Project of Hebei(20241093)

Abstract:

Objective The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. Methods Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC50) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. Results Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC50 of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). Conclusion CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.

Key words: cannabinoid receptor, autoimmune diseases, pemphigus, desmoglein, HaCaT cell

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