RETRACTED ARTICLE: MicroRNA-93 regulates the neurological function, cerebral edema and neuronal apoptosis of rats with intracerebral hemorrhage through TLR4/NF-κB signaling pathway

Abstract

In recent years, many studies have unraveled the impact of microRNAs (miRNAs) in intracerebral hemorrhage (ICH). This study aims to explore the role of miR-93 in modulating neurological function, cerebral edema and neuronal apoptosis of rats with ICH by regulating TLR4/NF-κB signaling pathway. ICH models were constructed using Ⅶ collagenase method. The successfully modeled rats were injected with miR-93 antagomir, TLR4/NF-κB signaling pathway activator or inhibitor together with their controls. The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF) was measured using enzyme-linked immunosorbent assay (ELISA). The expression of human aquaporin 4 (AQP-4), Caspase-3, Bax, Bcl-2 and TLR4/NF-κB signaling pathway-related proteins was also measured. MiR-93, TLR4 and NF-κB were all highly expressed in ICH, reduced miR-93 and inhibited TLR4/NF-κB signaling pathway could improve neurological function and suppress inflammation in ICH rats. Moreover, down-regulated miR-93 and suppressed TLR4/NF-κB signaling pathway were able to attenuate cerebral edema and abate pathological lesion. We have also found in this research that miR-93 knockdown as well as inhibited TLR4/NF-κB signaling pathway could relieve neuronal apoptosis in ICH rats. This study suggests that reduced miR-93 alleviates the neurological function and cerebral edema as well as repressed neuronal apoptosis of ICH rats via the inhibited activation of TLR4/NF-κB signaling pathway.

Acupuncture Attenuates Inflammation in Microglia of Vascular Dementia Rats by Inhibiting miR-93-Mediated TLR4/MyD88/NF-κB Signaling Pathway

“…Liu et al showed that miR-93 attenuated inflammation caused by acute myocardial infarction via regulating the expression of TLR4 [ 24 ]. Another research revealed that miR-93 antagomir could notably alleviate inflammation via reducing the expression of TLR4 and NF- κ B p65 in rats' brain tissues, indicating that miR-93 can positively regulate the TLR4 signaling pathway [ 23 ]. In line with these findings, we observed that a significant positive correlation existed between miR-93 and TLR4 levels, which implicates that miR-93 is likely to positively modulate the expression of TLR4 in hippocampus of 2VO rats.…”

“…In addition, one previous study revealed that miR-93 was increased in the serum of VD patients [ 21 ], implying that miR-93 may act as a potential therapeutic target for VD. Recently, lots of reports have indicated that miR-93 regulates inflammatory response by modulating TLR signaling pathways [ 23 , 24 ]. Ding et al reported that miR-93 regulated inflammation in osteoarthritis by targeting the TLR4/NF- κ B signaling pathway [ 25 ].…”

“…Ding et al reported that miR-93 regulated inflammation in osteoarthritis by targeting the TLR4/NF- κ B signaling pathway [ 25 ]. Shang et al revealed that miR-93 improved neurological function and inhibited inflammation in rats with cerebral hemorrhage through the TLR4/NF- κ B signaling pathway [ 23 ]. Consequently, regulation of the miR-93-mediated TLR signal pathway is probably a potential mechanism for alleviating the inflammatory response of VD.…”

Regulatory microRNAs and vascular cognitive impairment and dementia

“…By using endothelial cell‐specific miR‐126 conditional knockout mice, it was found that EC‐targeted deletion of miR‐126 aggravated cognitive impairment, decreased CBF, myelin density, and axon density, increased inflammation, and exacerbated water channel and glymphatic dysfunction compared with control mice in multiple microinfarction‐induced vascular dementia 101 . Recently, several groups have demonstrated that miR‐93 aggravates inflammatory response by modulating TLR signaling pathways 102,103 …”

Flaming the fight against cancer cells: the role of microRNA-93

“…A growing body of evidence demonstrates that miRs recognize their target genes by binding to the 3′-untranslated region [25][26][27]. Based on the role of miRs in biological processes, abnormal expression of miRs is associated with development of a number of pathologic events such as cancer [28,29], cardiovascular diseases [30,31] and neurological disorders (NDs) [32,33]. The alteration in expression leads to the application of miRs as biomarkers for identification of various pathological conditions, particularly cancer.…”