miR‑222 regulates brain injury and inflammation following intracerebral hemorrhage by targeting ITGB8

Abstract

intracerebral hemorrhage (icH) is a disease associated with high mortality and morbidity. Micrornas (mirnas) have been reported to be associated with the pathogenesis of numerous cerebrovascular diseases, including icH. mir-222 has been revealed to play important roles in various physiological and pathological processes in cardiovascular diseases. However, its role in icH remains largely unknown. The aim of the present study was to evaluate the potential effect of mir-222 on brain injury in icH. The results revealed that the expression of miR-222 was significantly increased in ICH, and downregulation of miR-222 significantly reduced erythrocyte lysate-induced cell apoptosis by decreasing the levels of cleaved caspase-3, cleaved caspase-9 and Bax and increasing the level of Bcl-2. in addition, downregulation of miR-222 suppressed the inflammatory responses in erythrocyte lysate-induced microglia, and inhibited inflammation, brain water content and improved neurological functions in icH mice. Mechanistically, integrin subunit β8 (iTGB8) was identified as a direct target of negative regulation by miR-222 in microglia cells, and up-regulation of iTGB8 led to the attenuation of inflammation and apoptosis. Collectively, the present findings indicated that miR-222 was a crucial regulator of inflammation via targeting of ITGB8, and represented a promising therapeutic strategy for icH.

Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

“…According to Chen et al [ 28 ], miR-222-5p has inhibitory effects on staphylococcal enterotoxin B-induced inflammatory response in lung injury. Also, Bai et al [ 29 ] showed that miR-222 possesses a regulatory role in brain injury and inflammation due to intracerebral hemorrhage. Moreover, miR-222-5p was downregulated in the SCI model, thus, suggesting miR-222-5p having a positive role in inhibiting LPS-mediated microglia cells apoptosis.…”

Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway

“…After TBI, inflammatory factors such as TNF- α , IL-1, and IL-6 are secreted and can induce oxidative stress responses and apoptosis, resulting in blood-brain barrier (BBB) impairment and cerebral oedema [ 17 – 19 ]. Though mild inflammation can protect the body, excessive inflammatory reactions aggravate the injury [ 20 ]. Therefore, inhibition of inflammation and oxidation plays an important role in neurological recovery after TBI, and new treatment methods must be explored.…”

Microglia: A Double-Edged Sword in Intracerebral Hemorrhage From Basic Mechanisms to Clinical Research

“…Recent studies have found that inhibition of miRNA-222 suppresses microglia-mediated inflammatory responses and improves neurological functions in a preclinical mouse model of ICH. Integrin subunit β8 (ITGB8) was identified as a directly negatively regulated target of miR−222 in microglial cells, leading to the attenuation of inflammation and apoptosis ( 54 ). Besides, miR-132 enhances the cholinergic blockade of the inflammatory response by targeting acetylcholinesterase (AChE), which also inhibits the activation of pro-inflammatory microglia and provides protection against neuronal death caused by ischemia ( 55 ).…”