A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS-and MPTP-induced neuroinflammation

作者：Ye, Yongyi; He, Xiaozheng; Lu, Fengfei; Mao, Hengxu; Zhu, Zhiyuan; Yao, Longping; Luo, Wanxian; Sun, Xiang; Wang, Baoyan; Qian, Chen; Zhang, Yizhou; Lu, Guohui^*; Zhang, Shizhong^*

来源：Cell Death & Disease, 2018, 9(8): 803.

DOI：10.1038/s41419-018-0821-5

• PROTEIN-KINASE-C
• PARKINSONS-DISEASE
• DOPAMINERGIC NEURODEGENERATION
• NONCODING RNAS
• LNCRNA GAS5
• P53
• INFLAMMATION
• PROMOTES
• MICRORNA
• MODELS

The role of microglial-mediated sustained neuroinflammation in the onset and progression of Parkinson's disease (PD) is well established, but the mechanisms contributing to microglial activation remain unclear. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated. Here, we report that lincRNA-p21 promotes microglial activation through a p53-dependent transcriptional pathway. We further demonstrate that lincRNA-p21 competitively binds to the miR-181 family and induces microglial activation through the miR-181/PKC-delta pathway. Moreover, PKC-delta induction further increases the expression of p53/lincRNA-p21 and thus forms a circuit. Taken together, our results suggest that p53/lincRNA-p21, together with miR-181/PKC-delta, form a double-negative feedback loop that facilitates sustained microglial activation and the deterioration of neurodegeneration.

• 出版日期2018-7-23
• 单位南方医科大学; 南昌大学