DGCR5 attenuates neuropathic pain through sponging miR‐330‐3p and regulating PDCD4 in CCI rat models

Peng, Chengwei; Zhang, Chuanqing; Su, Zhe; Lin, Dongyang

doi:10.1002/jcp.27487

Cited by 32 publications

(16 citation statements)

References 36 publications

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“…Elevated PDCD4 expression was observed in the rat spinal cord injury model [33], the chronic sciatic nerve injury (CCI)-induced rat neuropathic pain model [34], the oxygen-glucose deprivation/reoxygenation (OGDR) injury model of rat hippocampal neurons [35], and the ischemia and reperfusion (I/R)-induced neuronal lesion model in mice retinas [25]. The available studies indicate that PDCD4 may be extensively involved in neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation

Chen

Lü

Duan

et al. 2021

Preprint

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Neuroinflammation and neuron injury are common features of the central nervous system (CNS) diseases. It will be of great significance to identify their shared regulatory mechanisms and explore the potential therapeutic targets. Programmed cell death factor 4 (PDCD4), an apoptosis-related molecule, extensively participates in tumorigenesis and inflammatory diseases, but its expression and biological function during CNS neuroinflammation remain unclear. In the present study, utilizing the lipopolysaccharide (LPS)-induced neuroinflammation model on mice, we first reported an elevated expression of PDCD4 in both injured neurons and activated microglia of the inflamed mice brain. A similar change of PDCD4 expression was observed in the in vitro microglial activation model. Silencing PDCD4 by shRNA significantly inhibited the phosphorylation of MAPKs (p38, ERK, and JNK), prevented the phosphorylation and nuclear transportation of NF-κB p65, and thus attenuated the LPS-induced microglial inflammatory activation. Interestingly, LPS also required the MAPKs/NF-κB signaling activation to boost PDCD4 expression in microglia, and thus form a positive loop. Moreover, a persistent elevation of PDCD4 expression was detected in the H2O2-induced neuronal oxidative damage model. Knocking down PDCD4 significantly inhibited the expression of pro-apoptotic protein BAX, suggesting the pro-apoptotic activity of PDCD4 in the neuron. Taken together, our data indicated that PDCD4 may serve as a hub regulatory molecule that simultaneously promotes both the microglial inflammatory activation and the oxidative stress-induced neuronal apoptosis within CNS. The microglial PDCD4/MAPKs/NF-κB positive feedback loop may exaggerate the vicious cycle of neuroinflammation and neuronal injury, and thus may become potential therapeutic targets for neuroinflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation

Chen

Lü

Duan

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Chronic restraint stress increased PDCD4 expression in mice hippocampus by decreasing the mTORC1-mediated proteasomes degradation [32]. Elevated PDCD4 expression was observed in the rat spinal cord injury model [33], the chronic sciatic nerve injury (CCI)-induced rat neuropathic pain model [34], the oxygen-glucose deprivation/reoxygenation (OGDR) injury model of rat hippocampal neurons [35], and the ischemia and reperfusion (I/R)-induced neuronal lesion model in mouse retina [25]. The available studies have indicated that PDCD4 may be extensively involved in neuronal damage.…”

Section: Discussionmentioning

confidence: 99%

PDCD4–MAPK–NF-κB Positive Loop Simultaneously Promotes Microglia Activation and Neuron Apoptosis During Neuroinflammation

Chen

Lü

Duan

et al. 2021

Preprint

View full text Add to dashboard Cite

Neuroinflammation and neuron injury are common features of the central nervous system (CNS) diseases. It is of great significance to identify their shared regulatory mechanisms and explore the potential therapeutic targets. Programmed cell death factor 4 (PDCD4), an apoptosis-related molecule, extensively participates in tumorigenesis and inflammatory diseases, but its expression and biological function during CNS neuroinflammation remain unclear. In the present study, utilizing the lipopolysaccharide (LPS)-induced neuroinflammation model in mice, we reported an elevated expression of PDCD4 both in injured neurons and activated microglia of the inflamed brain. A similar change in PDCD4 expression was observed in vitro in the microglial activation model. Silencing PDCD4 by shRNA significantly inhibited the phosphorylation of MAPKs (p38, ERK, and JNK), prevented the phosphorylation and nuclear translocation of NF-κB p65, and thus attenuated the LPS-induced microglial inflammatory activation. Interestingly, LPS also required the MAPK/NF-κB signaling activation to boost PDCD4 expression in microglia, indicating the presence of a positive loop. Moreover, a persistent elevation of PDCD4 expression was detected in the H2O2-induced neuronal oxidative damage model. Knocking down PDCD4 significantly inhibited the expression of proapoptotic protein BAX, suggesting the proapoptotic activity of PDCD4 in neurons. Taken together, our data indicated that PDCD4 may serve as a hub regulatory molecule that simultaneously promotes the microglial inflammatory activation and the oxidative stress-induced neuronal apoptosis within CNS. The microglial PDCD4–MAPK–NF-κB positive feedback loop may exaggerate the vicious cycle of neuroinflammation and neuronal injury and thus may become a potential therapeutic target for neuroinflammatory diseases.

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“…They relieved hyperalgesia and decreased neuroinflammation by modulating the P2X 3 receptor or P2X 7 receptor. In addition to the lncRNAs reported above, some lncRNAs have also been reported to be associated with NP [19,[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138].…”

Section: Lncrnas and Npmentioning

confidence: 99%

“…Compared with sham CCI, the lncRNA DGCR5 was downregulated in the spinal cord of CCI rats. DGCR5 could negatively regulate the expression of miR-330-3p and suppress neuroinflammation and hyperalgesia by sponging miR-330-3p and modulating the downstream target PDCD4 [134]. Dou and colleagues [136] showed that the lncRNA CCAT1 was significantly decreased in the DRG, spinal cord, hippocampus, and anterior cingulate cortex of CCI rats.…”

Section: Interactions Among Lncrnas Mirnas and Mrnas In Npmentioning

confidence: 99%

Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain

et al. 2020

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Neuropathic pain (NP) is directly caused by an injury or disease of the somatosensory nervous system. It is a serious type of chronic pain that is a burden to the economy and public health. Although recent studies have improved our understanding of NP, its pathogenesis has not been fully elucidated. Noncoding RNAs, including lncRNAs, circRNAs, and miRNAs, are involved in the pathological development of NP through many mechanisms. In addition, extensive evidence suggests that novel regulatory mechanisms among lncRNAs/circRNAs, miRNAs, and mRNAs play a crucial role in the pathophysiological process of NP. In this review, we comprehensively summarize the regulatory relationship among lncRNAs/circRNAs, miRNAs, and mRNAs and emphasize the important role of the lncRNA/circRNA-miRNA-mRNA axis in NP.

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DGCR5 attenuates neuropathic pain through sponging miR‐330‐3p and regulating PDCD4 in CCI rat models

Cited by 32 publications

References 36 publications

PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation

PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation

PDCD4–MAPK–NF-κB Positive Loop Simultaneously Promotes Microglia Activation and Neuron Apoptosis During Neuroinflammation

Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain

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DGCR5 attenuates neuropathic pain through sponging miR‐330‐3p and regulating PDCD4 in CCI rat models

Cited by 32 publications

References 36 publications

PDCD4-MAPKs-NF-κB positive loop&nbsp;simultaneously&nbsp;promotes&nbsp;microglia activation and neuron apoptosis&nbsp;during&nbsp;neuroinflammation

PDCD4-MAPKs-NF-κB positive loop&nbsp;simultaneously&nbsp;promotes&nbsp;microglia activation and neuron apoptosis&nbsp;during&nbsp;neuroinflammation

PDCD4–MAPK–NF-κB Positive Loop Simultaneously Promotes Microglia Activation and Neuron Apoptosis During Neuroinflammation

Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain

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PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation

PDCD4-MAPKs-NF-κB positive loop simultaneously promotes microglia activation and neuron apoptosis during neuroinflammation