miR‐29c‐3p inhibits microglial NLRP3 inflammasome activation by targeting NFAT5 in Parkinson's disease

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 25; no. 6; pp. 364 - 374
• Main Authors: Wang, Ruili, Li, Qing, He, Ya, Yang, Ying, Ma, Qiaoya, Li, Chen
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2020
• Subjects: Animal models; Inflammasomes; Inflammation; Lipopolysaccharides; Microglia; miR‐29c‐3p; Movement disorders; Neurodegenerative diseases; NFAT5; NLRP3 inflammasome; Parkinson's disease; Therapeutic applications; NFAT5; Parkinson's disease; NLRP3 inflammasome; microglia; miR-29c-3p
• ISSN: 1356-9597; 1365-2443; 1365-2443
• DOI: 10.1111/gtc.12764

Microglial inflammation is identified as a key process associated with Parkinson's disease (PD) pathogenesis. Our previous study showed that miR‐29c‐3p (miR‐29c) exhibited anti‐inflammatory properties in PD animal and neuronal models. However, the specific role and regulatory mechanism of miR‐29c played in microglia are still unclear. In this study, lipopolysaccharide (LPS)‐stimulated BV‐2 cells were used to establish a cellular model of microglial activation for investigating PD. The results showed a decreased expression of miR‐29c in LPS‐induced BV‐2 cells. Over‐expression of miR‐29c suppressed LPS‐triggered Iba‐1 increment, pro‐inflammatory cytokine release, and NF‐кB and TXNIP/NLRP3 inflammasome activation. Silence of miR‐29c induced similar effects with LPS on microglial inflammation. In addition, we found that NFAT5 was negatively correlated with miR‐29c. Knockdown of NFAT5 blocked the aggravated inflammation in microglia treated by miR‐29c inhibitor. Thus, these findings suggest that miR‐29c modulates NLRP3 inflammasome to impair microglial inflammatory responses by targeting NFAT5, which represents a promising therapeutic target for PD. miR‐29c protects against microglial activation of PD. miR‐29c suppresses NLRP3 inflammasome activation by targeting NFAT5.