Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China.
Department of Hematology, The First People's Hospital of Yunnan Province, China.
Arch Biochem Biophys. 2024 Aug;758:110063. doi: 10.1016/j.abb.2024.110063. Epub 2024 Jun 14.
To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.
探讨 miR-34a 在干燥综合征（SS）中的潜在分子机制。
采用透射电镜观察轻、重度 SS 患者的唾液腺组织。构建 SS 小鼠模型，并注射 miR-34a 拮抗剂。将 miR-34a 模拟物转染入 HSGE 细胞。Starbase 预测 miR-34a 结合位点，并通过双荧光素酶报告实验进行验证。采用免疫组化、HE 染色、CCK-8、TUNEL 检测、流式细胞术、免疫荧光和 Western blot 检测 miR-34a 对 HSGE 细胞中 NF-κB 信号通路和线粒体凋亡途径的影响。
重度 SS 患者的唾液腺中出现明显的线粒体损伤和细胞凋亡。严重 SS 患者的唾液腺中 miR-34a 表达上调，NF-κB 信号通路被激活。抑制 miR-34a 可减轻 SS 小鼠的唾液腺损伤，同时抑制 NF-κB 信号通路和线粒体凋亡途径的激活。
miR-34a 通过靶向 IκBα 促进 NF-κB 信号通路，导致线粒体途径凋亡，并加重 SS 引起的唾液腺损伤。
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