Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood–Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B

Ge, Xintong; Li, Wenzhu; Huang, Shan; Yin, Zhenyu; Yang, Ming; Han, Zhaoxia; Han, Zhaoli; Chen, Fanglian; Wang, Haichen; Lei, Ping; Zhang, Jianning

doi:10.1089/neu.2018.5728

Cited by 60 publications

(53 citation statements)

References 57 publications

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“…The miR‐146a‐5p is induced in response to the microbial components and pro‐inflammatory cytokines and is involved in the control of TLR and cytokine signalling through a negative feedback regulation loops (Taganov, Boldin, Chang, & Baltimore, ). The miR‐155‐5p and miR‐21‐5p were also implicated in the induction of neuroinflammatory responses (Ge et al, ; Greco et al, ). We also detected increased phosphorylation of STAT1 (Tyr701) showing activation of STAT1 pro‐inflammatory pathway in M1 cells (Figure S2a).…”

Section: Resultsmentioning

confidence: 99%

Extracellular vesicles can act as a potent immunomodulators of human microglial cells

Jonavičė

Tunaitis

Kriaučiūnaitė

et al. 2019

J Tissue Eng Regen Med

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Functional impairments of microglia have been recently associated with several neurological conditions. Therefore, modulation of anti‐inflammatory and phagocytic properties of microglial cells could represent a novel therapeutic approach. In the present study, we investigated the effects of extracellular vesicles (EVs) derived from stem cells from the dental pulp of human exfoliated deciduous teeth (SHEDs) on the inflammatory response and functional properties of immortalized human microglial cells. NFκB reporter assays demonstrated that EVs suppressed LPS‐induced activation of NFκB signalling pathway in human microglial cells. The effect was similar to that obtained with anti‐TLR4 blocking antibody. We also show that EVs differentially affected phagocytic activity of unpolarized (M0) and polarized (M1 and M2) microglial cells. EVs induced significant upregulation of phagocytic activity in M0 cells (by 39%), slight decrease in M1 cells, and moderate increase (by 21%) in M2 cells. The Seahorse XF Glycolysis Stress Test revealed that EVs induced an immediate and sustained increase of glycolytic activity in M0, M1, and M2 cells. Interestingly, EVs acted in an inverse dose‐dependent manner. These findings indicate that EVs can induce glycolytic reprogramming of unpolarized and polarized human microglial cells. In conclusion, our pilot study demonstrates that EVs derived from SHEDs can act as a potent immunomodulators of human microglial cells. These findings could be potentially exploited for the development of new therapeutic strategies targeting neuroinflammatory microglia.

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Section: Resultsmentioning

confidence: 99%

Extracellular vesicles can act as a potent immunomodulators of human microglial cells

Jonavičė

Tunaitis

Kriaučiūnaitė

et al. 2019

J Tissue Eng Regen Med

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“…IL‐6 and MCP‐1 are important inflammatory cytokines in ARPE‐19 cells . MiR‐21‐3p reportedly increased inflammation of brain microvascular endothelial cells . Downregulation of miR‐21‐3p attenuates UV‐induced skin inflammation .…”

Section: Discussionmentioning

confidence: 99%

“…However, miR‐146a blocked inflammatory responses to attenuate cell injury mediated by high glucose in primary human retinal microvascular endothelial cells . MiR‐21‐3p promoted inflammation and apoptosis in brain microvascular endothelial cells . MiRs also are implicated in the inflammation and apoptosis of ARPE‐19 cells and are thus a focus of potential therapeutic of AMD.…”

Section: Introductionmentioning

confidence: 99%

MiR‐21‐3p modulates lipopolysaccharide‐induced inflammation and apoptosis via targeting TGS4 in retinal pigment epithelial cells

Liu

Ran

2019

Clin Exp Pharma Physio

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Age-related macular degeneration (AMD) is the most common cause of blindness and visual impairment in the elderly. 1 AMD is characterized by accumulation of yellow crystal deposits and loss of central vision due to degenerative changes in the macula. The integrity of the retina is strongly related to retinal pigment epithelial cells, which maintain the local extracellular environment. Morphological and functional abnormalities of these cells can lead to AMD. 2 Inflammation and apoptosis also play central roles in the pathophysiology of AMD. 3,4 Determining appropriate treatment for AMD is an important endeavour to increase patient quality of life.MicroRNAs (miRs) are a class of noncoding RNAs that can inhibit or degrade genetic targets by binding to their 3ʹ untranslated regions (UTRs). MiRs play integral roles in numerous disease processes, including oxidase stress, inflammation, and apoptosis. 5 For AbstractAge-related macular degeneration (AMD) is a major reason of blindness in the elderly.MicroRNAs are implicated in various pathological processes, including inflammation and apoptosis. In this study, we aim to investigate the biological functions of miR- 21-3p in inflammation and apoptosis caused by lipopolysaccharide (LPS) in humanretinal pigment epithelial (ARPE-19) cells. The miR-21-3p inhibitor and mimic were transfected into ARPE-19 cells for 48 hours, followed by exposed to LPS (10 μg/mL) for 24 hours. The mRNA and protein expression of IL-6 and MCP-1 were measured using real-time PCR (RT-PCR) and enzyme-linked immunosorbent assays. Cell viability, apoptosis, caspase 3 activity, cleaved caspase-3 and cleaved-PARP protein levels were detected to evaluate the effects of miR-21-3p on apoptosis. Additionally, the target relationship between miR-21-3p and regulator of G-protein signalling 4 (RGS4) was verified by dual luciferase reporter assay. RT-PCR analysis demonstrated that LPS induced miR-21-3p expression. Inhibition of miR-21-3p reduced the mRNA and protein levels of IL-6 and MCP-1. Apoptosis, caspase-3 activity, and cleaved-caspase 3 and cleaved PARP protein levels were repressed by the miR-21-3p inhibitor.However, overexpression of miR-21-3p showed the opposite results. Furthermore, we identified that miR-21-3p directly targeted the 3ʹ untranslated region of RGS4.MiR-21-3p negatively regulated the expression of RGS4 both in mRNA and protein levels. Silencing RGS4 reduced the anti-inflammatory and anti-apoptotic effects of miR-21-3p inhibitor. Our results revealed that miR-21-3p inhibition targeted RGS4 to attenuate inflammatory responses and apoptosis caused by LPS in ARPE-19 cells. K E Y W O R D Sapoptosis, inflammation, MiR-21-3p, RGS4

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“…This disease is the second most common neurodegenerative disorder following Alzheimer disease (1). Current evidence suggests that miRs are involved in diverse biological processes including pathogenesis of neurodegenerative disorders and abnormal brain function (8,14). With regard to PD, several miRs have been reported to participate and play important roles in PD progression, via the regulation of various processes, such as apoptosis, autophagy, inflammation, mitochondrial dysfunction, and ROS activity (15,16).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑21 suppresses 1‑methyl‑4‑phenylpyridinium‑induced neuronal damage in MES23.5 cells

Mao

Ding

2019

Exp Ther Med

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Accumulating evidence suggests that overproduction of oxidative stress, increases neuroinflammation and activates apoptosis. These two processes are associated with the development of Parkinson's disease (PD). The present study aimed to investigate the role of miR-21 in the development of PD. 1-Methyl-4-phenylpyridinium (MPP + ) was used to induce a PD-like model in MES23.5 cells. The results of the reverse transcription-quantitative PCR assays indicated that miR-21 levels were markedly increased in MES23.5 cells following MPP + treatment. Furthermore, MES23.5 cells were transfected with miR-21 inhibitor, mimics and/ or relevant negative control, following MPP + administration. The results of the functional assays revealed that downregulation of miR-21 significantly attenuated the induction of cell apoptosis and reactive oxygen species (ROS) production, while it enhanced the survival of MPP + -induced MES23.5 cells. Furthermore, downregulation of miR-21 increased the expression levels of tyrosine hydroxylase, whereas suppression of miR-21 inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, IL-1β and tumor necrosis factor-α] in MES23.5 cells. Western blot analysis further indicated that the Bcl-2/Bax protein expression ratio was significantly increased and double luciferase assay analysis confirmed that Bcl-2 was a direct target of miR-21. Taken collectively, the data demonstrated that downregulation of miR-21 protected cells from MPP + -mediated cytotoxicity by the inhibition of apoptosis induction, the reduction of the inflammatory response and the suppression of ROS production. The present findings may provide novel approaches for PD clinical treatment.

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Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood–Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B

Cited by 60 publications

References 57 publications

Extracellular vesicles can act as a potent immunomodulators of human microglial cells

Extracellular vesicles can act as a potent immunomodulators of human microglial cells

MiR‐21‐3p modulates lipopolysaccharide‐induced inflammation and apoptosis via targeting TGS4 in retinal pigment epithelial cells

Downregulation of miR‑21 suppresses 1‑methyl‑4‑phenylpyridinium‑induced neuronal damage in MES23.5 cells

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