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TRPV1 Suppressed NLRP3 Through Regulating Autophagy in Microglia After Ischemia-Reperfusion Injury

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Abstract

The microglia-mediated inflammatory response is one of the main causes of brain tissue damage after stroke. In recent years, it has been reported that autophagy in microglia played an important role in inflammatory response after stroke. Transient receptor potential vanilloid 1 (TRPV1) has been shown to regulate autophagy and inflammatory in microglia; however, the detailed mechanisms remain unclear. This study aimed to investigate whether autophagy regulates inflammatory is associated with TRPV1. Model of oxygen and glucose deprivation/reoxygenation (OGD/R) was established in vitro to induce cerebral ischemia-reperfusion injury (I/R). siRNA of Atg5, inhibitors, and agonists of both autophagy and TRPV1 were involved in our study. Autophagy was assayed by immunofluorescence staining LC-3 and autophagosome was observed using transmission electron microscopy (TEM). Autophagy/inflammation-related markers as Atg5, LC-3II/LC-3I, Beclin-1, NLRP3, IL-1β, and Caspase-1 were also measured in the present study. Results indicated that I/R injury-induced inflammatory injury may be impeded by inhibition of autophagy, and TRPV1 could suppress OGD/R-induced autophagy of microglia. However, the effect of TRPV1’s inhibitor on inflammatory response was attenuated when the autophagy was blocked. These findings suggested that TRPV1 exhibits an anti-inflammatory effect on OGD/R-induced microglia, which was at least correlated with the anti-autophagy action of TRPV1 partially.

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Data Availability

All data of this study are available on request from the corresponding author.

Abbreviations

OGD/R:

Oxygen-glucose deprivation/reoxygenation

DMSO:

Dimethyl sulfoxide

TRPV1:

Transient receptor potential vanilloid 1

NLRP3:

Nod-like receptor protein 3

RAPA:

Rapamycin

3-MA:

3-methyladenine

Iba1:

Ionized calcium-binding adapter molecule 1

LC-3:

Microtubule-associated protein 1 light chain 3

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Acknowledgements

This work was supported by the Wenzhou Municipal Science and Technology Bureau project funding (Y20180096) and the Natural Science Foundation of Zhejiang Province (LY20H170001).

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Authors and Affiliations

  1. The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road, Wenzhou, Zhejiang, China

    Yao Lin, Tingting Huang, Weimin Shen, Qiongyi Pang, Qingfeng Xie, Xiang Chen & Fengxia Tu

Authors
  1. Yao Lin
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  2. Tingting Huang
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  3. Weimin Shen
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  4. Qiongyi Pang
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  5. Qingfeng Xie
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  6. Xiang Chen
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  7. Fengxia Tu
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Contributions

Yao Lin: conceptualization, methodology, writing; Tingting Huang: visualization, data curation; Weimin Shen: investigation, data curation; Qiongyi Pang and Qingfeng Xie: investigation, visualization, and validation; Xiang Chen and Fengxia Tu: writing—reviewing and editing, supervision.

Corresponding authors

Correspondence to Xiang Chen or Fengxia Tu.

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All the animal experiments in our study have been approved by the Institutional Animal Care and Use Committee (IACUC) of Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.

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Not applicable.

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The authors declare no competing interests.

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Lin, Y., Huang, T., Shen, W. et al. TRPV1 Suppressed NLRP3 Through Regulating Autophagy in Microglia After Ischemia-Reperfusion Injury. J Mol Neurosci 72, 792–801 (2022). https://doi.org/10.1007/s12031-021-01935-2

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