MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

Abstract

Varicella zoster virus–induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice.

Exploration of altered miRNA expression and function in MSC-derived extracellular vesicles in response to hydatid antigen stimulation

“…This may be due to species variability or different cell type responses. Other miRNAs, such as miR-124, miR-206-3p, miR-1a-3p, miR-134, miR-23a-3p, miR-199, miR-486-5p, miR-210-3p, and miR-185, showed differential expression after antigenic stimulation and are known to be involved in immune regulation, inflammation, osteogenic differentiation, angiogenesis, and apoptosis ( Li et al, 2016 ; Huang and Zhu, 2018 ; Zhao et al, 2018 , 2023 ; Chen et al, 2019 , 2023 ; Chen J. X. et al, 2020 ; Ghafouri-Fard et al, 2021 ; Yang et al, 2021 ; Zhang Z. et al, 2021 ; Wang et al, 2022 ; Castaño et al, 2023 ; Dong et al, 2023 ; Li and Li, 2023 ; Liu et al, 2023 ; Ma et al, 2023 ; Su et al, 2023 ).…”

Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms

“…A recent study suggested that miR-29-enriched exosomes originate from stem cells and alleviate proinflammatory responses in an osteoarthritis in a rat model (Le et al, 2016). Similarly, miR-199-3p overexpression attenuated TRX-induced PHN by targeting MECP2 in mice (Wang et al, 2022). ExomiR-181c-5p was incorporated by microglial cells and prevented inflammatory substances from being released.…”

Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms

“… 121 Similarly, miR-199-3p overexpression in mice attenuated postherpetic neuralgia induced by TRX by targeting MECP2. 122 Microglial cells incorporated exomiR-181c-5p, which prevented the release of inflammatory substances. Intrathecal treatment with exomiR-181c-5p in CCI rats reduced neuroinflammatory symptoms and neuropathic pain.…”