Senescent epithelial cells remodel the microenvironment for the progression of oral submucous fibrosis through secreting TGF-β1

衰老上皮细胞通过分泌 TGF-β1 重塑口腔黏膜下纤维化进展的微环境

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作者:Zijia Wang, Ying Han, Ying Peng, Shuhui Shao, Huanquan Nie, Kun Xia, Haofeng Xiong, Tong Su

Conclusions

Senescent epithelial cells are involved in OSF progression and may become a promising target for OSF treatment.

Methods

The immunohistochemistry and Sudan black B staining were performed to identify epithelium senescence in OSF tissues. Arecoline was used to induce human oral keratinocytes (HOKs) senescence. The cell morphology, senescence-associated β galactosidase activity, cell counting Kit 8, immunofluorescence, quantitative real-time PCR, and western blot assay were used to identification of senescent HOKs. The enzyme-linked immunosorbent assay was exerted to evaluate the levels of transforming growth factor β1 (TGF-β1) in the supernatants of HOKs treated with or without arecoline.

Results

The senescence-associated markers, p16 and p21, were overexpressed in OSF epithelium. These expressions were correlated with alpha-smooth actin (α-SMA) positively and proliferating cell nuclear antigen (PCNA) negatively. Moreover, Sudan black staining showed that there was more lipofuscin in OSF epithelium. In vitro, HOKs treated with arecoline showed senescence-associated characteristics including enlarged and flattened morphology, senescence-associated β galactosidase staining, cell growth arrest, γH2A.X foci, upregulation of p53, p21, and TGF-β1 protein levels. Moreover, senescent HOKs secreted more TGF-β1. Conclusions: Senescent epithelial cells are involved in OSF progression and may become a promising target for OSF treatment.

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