circ_0002456/FUS interaction inhibits NF-κB signaling to attenuate DNA damage and inflammatory responses in hDPSCs

被引:0
作者
Lin, Liecong [1 ]
Dong, Huixian [1 ]
Lai, Feng [1 ]
Zhang, Jingkun [1 ]
Wang, Bingtao [1 ]
Lv, Xiaohui [1 ]
Lin, Li [1 ]
Hong, Kehuan [1 ]
Zhao, Yuxuan [1 ]
Jiang, Qianzhou [1 ]
机构
[1] Guangzhou Med Univ, Guangzhou Inst Oral Dis, Key Lab Oral Med, Stomatol Hosp, Huangsha Ave 39, Guangzhou 510000, Peoples R China
基金
中国国家自然科学基金;
关键词
CircRNA; DNA damage; Pulpitis; FUS; NF-kappa B; PATHWAY;
D O I
10.1186/s13287-025-04391-6
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Objectivescircular RNAs (circRNAs) are emerging regulators of inflammatory diseases, but their role in pulpitis remains unclear. This study aimed to investigate the role of circRNA in the occurrence and development of pulpitis.MethodsqRT-PCR and Western Blot were used to detect gamma-H2AX, a marker of DNA double-strand breaks (DSBs), and inflammatory factors in pulp tissues. Bioinformatics identified dysregulated circRNAs. Loss- and gain-of-function experiments were conducted to explore the function of circ_0002456 in lipopolysaccharide (LPS)-induced DNA damage and inflammation in human dental pulp stem cells (hDPSCs). The interaction between circ_0002456 and fused in sarcoma (FUS) protein was validated by RNA fluorescence in situ hybridization (FISH), RNA pull-down and nucleoplasmic separation experimen. NF-kappa B pathway activation was assessed after circ_0002456/FUS siRNA transfection in hDPSCs, and NF-kappa B inhibitors were used to confirm its regulatory role in DNA damage and inflammation.ResultsDNA damage was positively correlated with inflammation in pulpitis. In vitro, circ_0002456 downregulation exacerbated LPS-induced DNA damage and inflammation, while overexpression alleviated these effects. Mechanistically, circ_0002456 bound FUS, restricting its nuclear export and suppressing NF-kappa B activation, thereby mitigating DNA damage and inflammation.Conclusioncirc_0002456 interacts with FUS to inhibit NF-kappa B signaling, attenuating DNA damage and inflammation in hDPSCs, revealing a novel regulatory axis in pulpitis.
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页数:19
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