MiRNA-494 enhances M1 macrophage polarization via Nrdp1 in ICH mice model.

J Inflamm (Lond)

2Department of Neurology and Chongqing key laboratory of cerebravascular disease, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160 China.

Published: April 2020

Background: Ubiquitination-mediated M1/M2 macrophage polarization plays important roles in the pathogenesis of immune disease. However, the regulatory mechanism of ubiquitination during M1/M2 macrophage polarization following intracerebral hemorrhage (ICH) has not been well studied.

Methods: In the experiment, macrophages were administered with erythrocyte lysates, and then miR-494-, Nrdp1-, and M1/M2-related markers were analyzed. Brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed.

Results: We found that miR-494 levels increased while Nrdp1 levels decreased in macrophages after ICH. We also demonstrated that miR-494 inhibited Nrdp1 expression by directly binding its 3'-untranslated region. MiR-494 attenuated C/EBP-β activation and downstream proinflammatory factor production. Upregulation of Nrdp1 in macrophages significantly promoted M2 macrophage polarization via ubiquitinating and activating C/EBP-β. Moreover, the results indicated that miR-494 could enhance M1 macrophage polarization, promote brain edema, and impair neurological functions in ICH mice.

Conclusions: Taken together, our results demonstrated that Nrdp1 contributed to M1/M2 macrophage polarization and neuroinflammation via ubiquitination and activation of C/EBP-β in ICH. miR-494 may provide a promising therapeutic clue for ICH.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183644PMC
http://dx.doi.org/10.1186/s12950-020-00247-3DOI Listing

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