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

Cell Death and Disease - Tập 9 Số 8
Yongyi Ye1, Xiaozheng He1, Fengfei Lu1, Hengxu Mao1, Zhiyuan Zhu1, Longping Yao1, Wanxian Luo2, Xiang Sun1, Baoyan Wang1, Yizhou Zhang3, Guohui Lu4, Shizhong Zhang1
1The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, China
2Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China
3Tarbut V'torah Community Day School, Irvine, CA, 92603, USA
4Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, 330006, Nanchang, China

Tóm tắt

AbstractThe 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-δ pathway. Moreover, PKC-δ 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-δ, form a double-negative feedback loop that facilitates sustained microglial activation and the deterioration of neurodegeneration.

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Cell Death and Disease

Tập 9 Số 8

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