miR‑30e‑5p attenuates neuronal deficit and inflammation of rats with intracerebral hemorrhage by regulating TLR4

Abstract

microRNAs (miRNAs or miRs) have been reported to regulate the pathology of intracerebral hemorrhage (ICH). Therefore, the present study aimed to investigate the function of miR-30e-5p in rats with ICH with specific focus on Toll-like receptor (TLR)4. In the present study, collagenase type IV was used for the establishment of the ICH model in rats, prior to which the rats were injected with miR-30e-5p mimic or miR-30e-5p mimic + pcDNA3.1-TLR4 plasmid. The expression levels of miR-30e-5p and TLR4 were then measured using reverse transcription-quantitative PCR and western blotting. The potential interaction between miR-30e-5p and TLR4 was tested using the MicroRNA Target Prediction Database and dual-luciferase reporter and RNA immunoprecipitation assay. In addition, the concentration of TNF-α, IL-6 and IL-1β was measured using ELISA. The protein expression levels of TLR4/myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling-associated molecules were measured by western blotting. Following induction of ICH, miR-30e-5p expression was downregulated, while TLR4 expression was upregulated. By contrast, injection with miR-30e-5p mimic rescued neuronal function while suppressing neuronal inflammation in rats following ICH; these effects were reversed by co-overexpression of TLR4. Furthermore, overexpression of miR-30e-5p inactivated TLR4/MyD88/TRIF signaling in rats with ICH; this was also reversed by overexpression of TLR4. Taken together, these results suggested that overexpression of miR-30e-5p exerted a protective role against neuronal deficit and inflammation caused by ICH in rats by targeting TLR4 and inactivating TLR4/MyD88/TRIF signaling.

Cisplatin induces acute kidney injury by downregulating miR‐30e‐5p that targets Galnt3 to activate the AMPK signaling pathway

“…One study found that miR-30e-5p could attenuate neuronal deficits and inflammation in rats with cerebral hemorrhage via TLR4. 15 Liu et al 14 demonstrated that the lack of miR-30e-5p could be involved in inflammation in rheumatoid arthritis by regulating the expression of Atl2. In addition, it has been shown that miR-30e-5p can be used as a biomarker for human kidney disease.…”

“…Chen et al 11 found that miR‐30e‐5p could alleviate inflammation and cardiac insufficiency after myocardial infarction by targeting phosphatase and tensin homolog (PTEN). One study found that miR‐30e‐5p could attenuate neuronal deficits and inflammation in rats with cerebral hemorrhage via TLR4 15 . Liu et al 14 demonstrated that the lack of miR‐30e‐5p could be involved in inflammation in rheumatoid arthritis by regulating the expression of Atl2.…”

“…Thus, miRNAs are considered to be early biological markers for AKI, and some miRNAs are potential therapeutic targets for AKI 9,10 . Several studies found that miR‐30e‐5p is fundamentally associated with a variety of inflammatory diseases, including rheumatoid arthritis, neuronal inflammation, systemic sclerosis, and systemic lupus erythematosus, and miR‐30e‐5p can be used as a biomarker for various human renal diseases 11–15 …”

“…9,10 Several studies found that miR-30e-5p is fundamentally associated with a variety of inflammatory diseases, including rheumatoid arthritis, neuronal inflammation, systemic sclerosis, and systemic lupus erythematosus, and miR-30e-5p can be used as a biomarker for various human renal diseases. [11][12][13][14][15] Recently, nanodrug delivery systems have been widely studied as an emerging drug delivery method. In addition to being an effective drug delivery platform, nanodrug delivery systems exhibit excellent biological properties.…”

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

“…In recent years, more and more evidence has suggested that the inflammatory response of the nervous system is throughout in EBI and DBI, especially playing a key role in the pathogenesis of EBI [ 41 , 42 , 43 ]. Studies have demonstrated that the TLR4- mediated signal pathway exerts an important effect on the inflammatory process of the nervous system after SAH [ 44 , 45 , 46 ]. Furthermore, in animal experiments, it was found that the inflammatory response after SAH can be reduced by inhibiting the TLR4-mediated signaling pathway, which alleviates EBI after SAH, thus improving the prognosis [ 4 , 17 , 20 , 32 , 47 , 48 ].…”