EGR1调控PDE12介导的线粒体功能障碍，从而诱导口腔黏膜下纤维化中口腔黏膜上皮屏障损伤
EGR1 regulates PDE12 mediated mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.
摘要(中文译文)
口腔黏膜下纤维化（OSF）的治疗因其复杂的发病机制而具有挑战性。其特征为上皮下胶原过度沉积并伴有上皮损伤。咀嚼槟榔被认为是OSF的主要病因。我们此前发现，磷酸二酯酶12（PDE12）参与口腔黏膜上皮屏障损伤，促进OSF的发生。早期生长反应因子1（EGR1）是一种特征明确的转录因子，已被认为与纤维化疾病（包括口腔纤维化）的发生发展有关。本研究旨在探讨PDE12过表达对OSF中口腔上皮细胞的影响及其潜在机制。我们采用PDE12过表达策略，验证其在HOK细胞线粒体功能障碍和口腔黏膜上皮屏障破坏中的关键作用。随后，通过电泳迁移率变动分析和染色质免疫沉淀分析，证实EGR1与PDE12基因启动子相互作用，从而上调其在HOK细胞中的表达。通过结合EGR1沉默和PDE12过表达策略，本研究证实PDE12诱导的线粒体功能和口腔黏膜上皮屏障损伤依赖于EGR1。这些发现表明，通过EGR1调控PDE12的表达可减轻槟榔碱诱导的上皮损伤，从而抑制OSF的发展，为对抗OSF提供了一种潜在的治疗策略。
Abstract
The treatment of oral submucosal fibrosis (OSF) is challenging owing to the complex pathogenesis. It is characterized by excessive collagen deposition in the subepithelium along with epithelial damage. Betel nut chewing is considered a major cause of OSF. We previously found that phosphodiesterase 12 (PDE12) was involved in the oral mucosal epithelial barrier damage, promoting the occurrence of OSF. Early growth response 1 (EGR1), a well-characterized transcription factor, has been implicated in the development of fibrotic diseases, including oral fibrosis. This study aimed to explore the effects and underlying mechanisms of PDE12 overexpression on oral epithelial cells in OSF. Overexpression of PDE12 was employed to verify its critical role in mitochondrial dysfunction and oral mucosal epithelial barrier disruption in HOKs. Subsequently, electrophoretic mobility shift assay and chromatin immunoprecipitation analysis were performed to demonstrate that EGR1 interacted with the promoter of the PDE12 gene, thereby upregulating its expression in HOKs. By combining EGR1 silencing and PDE12 overexpressing strategies, our study confirmed that PDE12-induced impairment of mitochondrial function and oral mucosal epithelial barrier was dependent on EGR1. These findings suggest that regulating the expression of PDE12 through EGR1 could alleviate arecoline-induced epithelial injury, thereby inhibiting the development of OSF and offering a potential therapeutic strategy to combat OSF.
如何引用
AMA
Jing Peng, Linlin Chen, Jinmei Xie, Xi Wang, Xuerou Wang, Cailian Chen, et al. EGR1 regulates PDE12 mediated mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.. European journal of pharmacology. 2026; doi:10.1016/j.ejphar.2026.178865.
APA
Jing Peng, Linlin Chen, Jinmei Xie, Xi Wang, Xuerou Wang, Cailian Chen, et al (2026). EGR1 regulates PDE12 mediated mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.. European journal of pharmacology. https://doi.org/10.1016/j.ejphar.2026.178865
GB/T 7714
Jing Peng, Linlin Chen, Jinmei Xie, Xi Wang, Xuerou Wang, Cailian Chen, et al. EGR1 regulates PDE12 mediated mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.[J]. European journal of pharmacology, 2026 doi:10.1016/j.ejphar.2026.178865.
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