NLRP6 contributes to inflammation and brain injury following intracerebral haemorrhage by activating autophagy
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ORIGINAL ARTICLE
NLRP6 contributes to inflammation and brain injury following intracerebral haemorrhage by activating autophagy Han Xiao 1,2,3 & Hui Chen 1,2,3 & Rong Jiang 4 & Li Zhang 1,2,3 & Lu Wang 1,2,3 & Hui Gan 1,2,3,5 & Ning Jiang 3,6 & Jing Zhao 3,5 & Xuan Zhai 1,2,3 & Ping Liang 1,2,3 Received: 4 November 2019 / Revised: 28 July 2020 / Accepted: 7 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Inflammation is a crucial factor contributing to secondary brain injury after intracerebral haemorrhage (ICH). NLRP6, a member of nod-like receptors (NLRs) family, has been reported to participate in inflammation and host-defence in multiple diseases. Distinct from the other NLR family members, NLRP6 regulates inflammation in an inflammasomedependent as well as an inflammasome-independent pathway. However, the role of NLRP6 in regulating signalling pathways during ICH is poorly understood. In the present study, we demonstrated that NLRP6 expression was upregulated after ICH, both in humans and in rats. Subsequently, we developed a rat model of ICH and found that NLRP6 knockdown reduced brain injury, alleviated inflammation, and suppressed autophagy following ICH. Further, results indicated that autophagy involved in NLRP6 mediated inflammation after ICH. Moreover, we found that NLRP6 mediated regulation of autophagy and inflammation was inflammasome-dependent. This study revealed the underlying molecular mechanism of NLRP6 in inflammation and highlights the therapeutic potential of targeting NLRP6 in secondary brain injury after ICH. Key messages • NLRP6 was upregulated following ICH in humans and rats. • NLRP6 knockdown reduced brain injury, alleviated inflammation, and suppressed autophagy following ICH. • NLRP6 aggravated inflammation after ICH by activating autophagy. • NLRP6 regulated inflammation and autophagy after ICH by activating inflammasome pathway. Keywords Intracerebral haemorrhage . Inflammation . NLRP6 . Autophagy . Inflammasome
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00109-020-01962-3) contains supplementary material, which is available to authorized users. * Ping Liang [email protected]
3
Institute of Neuroscience, Chongqing Medical University, Chongqing, China
1
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Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China
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Department of Pathophysiology, Chongqing Medical University, Chongqing, China
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Department of Pathology, Chongqing Medical University, Chongqing, China
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Department of Neurosurgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China
J Mol Med
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