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A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice

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Abstract

C-type lectin–like receptor 2 (CLEC-2) is a platelet surface–activating receptor with the prominent involvement in platelet activation, which was found to be associated with the progression and prognosis of acute ischemic stroke patients. Although podoplanin is the only known endogenous ligand for CLEC-2, the role of podoplanin/CLEC-2 in cerebral ischemia injury was unclear. In this study, we examined their role by using a mouse middle cerebral artery occlusion (MCAO) model. The expression of CLEC-2 and podoplanin increased after ischemia/reperfusion (I/R) injury, peaked at 24 h, and then decreased gradually. Podoplanin and CLEC-2 co-localized mainly in the ischemia/reperfusion cortex and expressed on neurons and microglia. Anti-podoplanin antibody pretreatment reduced cerebral infarct volume from 52.67 ± 4.67 to 34.08 ± 6.04% (P < 0.05) and attenuated the neurological deficits during acute stage and recovery stage. Moreover, a significant decrease of IL-18 and IL-1β was observed in the mice pretreated with the anti-podoplanin antibody. Our results demonstrate that the podoplanin-CLEC-2 axis might play an important role in cerebral ischemia/reperfusion injury in mice by promoting inflammatory reactions.

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Acknowledgements

This study was supported with the grants from the Second Affiliated Hospital of Soochow University Pre-Research Project of National Natural Science Foundation (SDFEYGJ1804), the opening project of Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases (KJS1859), the Suzhou Scientific and Technological Projects of People’s Livelihood-Basic Research on Medical and Health Application (SYS2019066), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX19_0814), and the National Natural Science Foundation of China (81601154).

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  1. Department of Neurology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China

    Danyang Meng, Xuechun Wu, Yongjun Cao & Xia Zhang

  2. Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou, 215123, China

    Danyang Meng, Xiaohua Ma & Zhigang Miao

  3. Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Hui Li

  4. Jiangsu Key Laboratory of Neuropsychiatric Diseases, Soochow University, Suzhou, 215123, Jiangsu,, China

    Zhigang Miao

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  1. Danyang Meng
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Meng, D., Ma, X., Li, H. et al. A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice. Neurotox Res 39, 477–488 (2021). https://doi.org/10.1007/s12640-020-00295-w

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