MiR-26a inhibits the inflammatory response of microglia by targeting HMGA2 in intracerebral hemorrhage

Abstract

Objective Intracerebral hemorrhage (ICH) is a common cerebrovascular disease with high mortality and poor prognosis. Therefore, the biological function and underlying molecular mechanism of miR-26a in inflammatory injury following ICH was investigated. Methods The potential role of miR-26a was investigated in lipopolysaccharide (LPS)-treated microglial cells by quantitative real-time PCR. To explore the potential role of HMGA2 in the miR-26a-regulated inflammatory response, LPS-induced microglial cells were cotransfected with an miR-26a mimic and pcDNA-HMGA2. Then, lentivirus-mediated overexpression of an miR-26a mimic in mouse microglial cells was performed, and the effects of miR-26a treatment on IL-6, IL-1β, and TNF-α expression in the mouse brain, neurological behavior, and rotarod test performance of mice after ICH were observed. Results MiR-26a was significantly downregulated in LPS-treated microglia and ICH mouse models. MiR-26a markedly reduced IL-6, IL-1β, and TNF-α expression in LPS-treated microglial cells. Furthermore, HMGA2 was verified as a direct target of miR-26a. In vivo, miR-26a overexpression in mouse microglial cells significantly suppressed proinflammatory cytokine expression in mouse brains and markedly improved the neurological behavior and rotarod test performance of mice after ICH. Conclusion MiR-26a remarkably inhibited proinflammatory cytokine release by targeting HMGA2, indicating that miR-26a could protect against secondary brain injury following ICH.

MiR-26a Reduces Inflammatory Responses via Inhibition of PGE2 Production by Targeting COX-2

“…In our study, we showed that the expression levels of miR-26a were downregulated following LPS stimulation, indicating that miR-26a may be involved in macrophage regulation. Furthermore, overexpression of miR-26a was associated with a significant decrease in the production of TNF-α, IL-6, and IL-1β, while knockdown of miR-26a exhibited a reverse effect in regulating the production of these proteins, consistent with previous research [ 20 , 39 ]. However, it is regrettable that there is a relatively modest effect in survival outcomes from mice with LPS-induced excessive inflammation after miR-26a administration.…”

“…Importantly, this downregulation was associated with increased IL-6 expression [ 19 ]. Subsequently, miR-26a was found to markedly reduce IL-6, IL-1β, and TNF-α expression by targeting high-mobility group AT-hook 2 in lipopolysaccharide (LPS)-treated microglial cells [ 20 ]. Furthermore, miR-26a overexpression in mouse microglial cells significantly suppressed pro-inflammatory cytokine expression in mouse brains and markedly improved the neurological behavior and rotarod test performance of mice after intracerebral hemorrhage.…”

Clock Gene Nr1d1 Alleviates Retinal Inflammation Through Repression of Hmga2 in Microglia

“… 18 In addition, Jin et al found that miR-26a inhibits the inflammatory responses of microglia by targeting HMGA2 in intracerebral hemorrhage. 17 Consistently, these results indicate that Hmga2 promotes LPS-induced inflammation through the NF-κB pathway in BV2 cells.…”

“…15 Moreover, HMGA2 is a driver of inflammation in conditions such as acute liver injury, intracerebral hemorrhage and cardiac dysfunction. [16][17][18] However, its role in retinal inflammation and whether Nr1d1 can regulate it should be investigated further.…”

Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage

“…There should be a 15-min rest interval between each test ( 46 ). Before surgery, the baseline of rats is around 150 s ( 86 ), while the mice are around 250~300 s ( 45 , 87 ). Animals with hemorrhagic damage tend to fall faster than normal ones ( 88 ).…”