MiR-34a promotes mitochondrial pathway of apoptosis in human salivary gland epithelial cells by activating NF-κB signaling.

Autor: He F; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Yu J; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Ma S; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Zhao W; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Wang Q; Department of Hematology, The First People's Hospital of Yunnan Province, China., He H; Department of Hematology, The First People's Hospital of Yunnan Province, China., Zhang M; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Wang J; Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, China., Lu Z; Department of Hematology, The First People's Hospital of Yunnan Province, China. Electronic address: lzx1806@126.com.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Aug; Vol. 758, pp. 110063. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1016/j.abb.2024.110063
Abstrakt: 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.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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