Oral lichen planus (OLP) is a kind of oral epithelial disorder featured with keratinocyte apoptosis and inflammatory reaction. The pathogenesis of OLP remains an enigma. Herein, we showed that the levels of miR-26a/b were robustly down-regulated in oral mucosal biopsies, serum and saliva in OLP patients compared with healthy control. Moreover, we found the binding sites of vitamin D receptor (VDR) in the promoter regions of miR-26a/b genes and proved that the induction of miR-26a/b was VDR dependent. The reduction of miR-26a/b expression was also detected in the oral epithelium of vitamin D deficient or VDR knockout mice. miR-26a/b inhibitors enhanced apoptosis and Type 1T helper (Th1) cells-related cytokines production in oral keratinocytes, whereas miR-26a/b mimics were protective. Mechanistically, we analyzed miRNA target genes and confirmed that miR-26a/b blocked apoptosis by directly targeting Protein Kinase C δ (PKCδ) which promotes cellular apoptotic processes. Meanwhile, miR-26a/b suppressed Th1-related cytokines secretion through targeting cluster of the differentiation 38 (CD38). In accordant with miR-26a/b decreases, PKCδ and CD38 levels were highly elevated in OLP patients' samples. Taken together, our present investigations suggest that vitamin D/VDR-induced miR-26a/b take protective functions in OLP via both inhibiting apoptosis and impeding inflammatory response in oral keratinocytes.

中文翻译：

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MicroRNA-26a / b在口腔扁平苔藓中具有保护作用。

口腔扁平苔藓（OLP）是一种以角质形成细胞凋亡和炎症反应为特征的口腔上皮疾病。OLP的发病机制仍是一个谜。本文中，我们显示与健康对照组相比，OLP患者的口腔黏膜活检，血清和唾液中的miR-26a / b水平被强烈下调。此外，我们在miR-26a / b基因的启动子区域发现了维生素D受体（VDR）的结合位点，并证明miR-26a / b的诱导是VDR依赖性的。在维生素D缺乏或VDR敲除小鼠的口腔上皮中也检测到miR-26a / b表达的降低。miR-26a / b抑制剂可增强口腔角质形成细胞的凋亡和1T辅助型（Th1）细胞相关细胞因子的产生，而miR-26a / b模仿物具有保护作用。机械上，我们分析了miRNA靶基因，并确认miR-26a / b通过直接靶向促进细胞凋亡过程的蛋白激酶Cδ（PKCδ）来阻止细胞凋亡。同时，miR-26a / b通过靶向分化簇38（CD38）抑制了Th1相关细胞因子的分泌。与miR-26a / b降低一致，OLP患者样品中PKCδ和CD38水平高度升高。综上所述，我们目前的研究表明，维生素D / VDR诱导的miR-26a / b通过抑制口腔角质形成细胞的凋亡和炎症反应，在OLP中发挥保护作用。miR-26a / b通过靶向分化38（CD38）簇抑制了Th1相关细胞因子的分泌。与miR-26a / b降低一致，OLP患者样品中PKCδ和CD38水平高度升高。综上所述，我们目前的研究表明，维生素D / VDR诱导的miR-26a / b通过抑制口腔角质形成细胞的凋亡和炎症反应，在OLP中发挥保护作用。miR-26a / b通过靶向分化38（CD38）簇抑制了Th1相关细胞因子的分泌。与miR-26a / b降低一致，OLP患者样品中PKCδ和CD38水平高度升高。综上所述，我们目前的研究表明，维生素D / VDR诱导的miR-26a / b通过抑制口腔角质形成细胞的凋亡和炎症反应，在OLP中发挥保护作用。