MiR‐377 Regulates Inflammation and Angiogenesis in Rats After Cerebral Ischemic Injury

Abstract

Ischemic stroke is the leading cause of disabilities worldwide. MicroRNA-377 (miR-377) plays important roles in ischemic injury. The present study focused on the mechanisms of miR-377 in protecting ischemic brain injury in rats. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. Primary rat microglial cells and brain microvascular endothelial cells (BMECs) were exposed to oxygen-glucose deprivation (OGD). The concentrations of cytokines (TNF-α, IL-1β, IL-6, IFN-γ, TGF-β, MMP2, COX2, and iNOS) in the culture medium were measured by specific ELISA. Tube formation assay was for the in vitro study of angiogenesis. Luciferase reporter assay was performed to confirm whether VEGF and EGR2 were direct targets of miR-377. The MCAO rats were intracerebroventricular (ICV) injection of miR-377 inhibitor to assess its protective effects in vivo. MiR-377 levels were decreased in the rat brain tissues at 1, 3, and 7 d after MCAO. Both microglia cells and BMECs under OGD showed markedly lower expression levels of miR-377 while higher expression levels of EGR2 and VEGF compared to those under normoxia conditions. Knockdown of miR-377 inhibited microglial activation and the release of pro-inflammatory cytokines after OGD. Suppression of miR-377 promoted the capillary-like tube formation and cell proliferation and migration of BMECs. The anti-inflammation effect of EGR2 and the angiogenesis effect of VEGF were regulated by miR-377 after OGD. Inhibition of miR-377 decreased cerebral infarct volume and suppressed cerebral inflammation but promoted angiogenesis in MCAO rats. Knockdown of miR-377 lessened the ischemic brain injury through promoting angiogenesis and suppressing cerebral inflammation. J. Cell. Biochem. 119: 327-337, 2018. © 2017 Wiley Periodicals, Inc.

RETRACTED ARTICLE: Mirt2 functions in synergy with miR-377 to participate in inflammatory pathophysiology of Sjögren's syndrome

“…Besides, Mirt2 overexpression restored the level of miR-377 which was repressed by IFN-c. miR-377 has been reported to promote white adipose tissue inflammation in mice models [16]. Besides, miR-377 relieves the cerebral inflammation and thereby lessens the ischemic brain injuries [15]. Similar results were observed in renal ischemia-reperfusion injury mice model [16] and retinal endothelial cell model [26].…”

“…Consistently, our results showed that enforcing Mirt2 expression protected SGECs against IFN-c-induced inflammatory insults. Given that miR-377 has been reported to regulate inflammation in cerebral ischemic injury rats model [15], we consequently focused on the regulatory relationship between miR-377 and Mirt2 in the biological progresses. It was noteworthy that Mirt2 protected SGECs against inflammatory insults by elevating miR-377.…”

“…Besides, miR-377 has been found to mediate the proliferation and apoptosis progresses as well as DNA methylation in several malignancies [12][13][14]. Its modulatory functions on inflammation have been revealed in recent studies [15,16]. Furthermore, miR-377 has been verified as a crucial mediator for pterostibene and allopurinol in response to the fructose-induced podocyte oxidative stress and inflammation [17].…”

δ-Opioid Receptors, microRNAs, and Neuroinflammation in Cerebral Ischemia/Hypoxia

“…MiR-377 plays a proinflammatory role following ischemic stroke by modulating the anti-inflammation effect of EGR2 and the proangiogenesis effect of vascular endothelial growth factor (VEGF) (71). Fan et al (71) found that the level of miR-377 decreased in the rat brain after MCAO and cultured microglia cells exposed to OGD. Furthermore, they found that miR-377 knockdown could attenuate microglia activation and the release of proinflammatory cytokines after OGD.…”

Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study

“…microRNAs (miRNAs), a family of highly conserved small non-coding RNAs directly binding to the 3′-untranslated regions (3′-UTRs), could mediate target genes, protein expression, and signaling pathways to affect cell functions such as proliferation, apoptosis, differentiation, migration, and invasion, thereby contributing to multiple biological processes, such as inflammation formation and immune response. [5][6][7][8] Accumulating evidences have proven that several miRNAs have established their value on the progress of various immune diseases, including RA, systemic lupus erythematosus (SLE), and psoriasis, which uncovered the potential of miRNA as marker for RA progression and prognosis. [9][10][11][12][13][14][15] However, no studies investigate the effect of comprehensive miRNA expression profile on predicting clinical response to TNF inhibitor in RA patients.…”