SENP1 modulates microglia‐mediated neuroinflammation toward intermittent hypoxia‐induced cognitive decline through the de‐SUMOylation of NEMO

Wang, Hongwei; Yang, Tianyun; Sun, Jinyuan; Zhang, Sisen; Liu, Song

doi:10.1111/jcmm.16689

Cited by 12 publications

(11 citation statements)

References 52 publications

(119 reference statements)

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“…Since the majority of literature focused on the IHdependent ROS generation responsible for microglial activation, 9,43 we investigated here inflammatory markers. Previous data have shown NF-κB activation in BV-2 44 following IH treatments.…”

Section: Discussionmentioning

confidence: 80%

“…Since the majority of literature focused on the IH‐dependent ROS generation responsible for microglial activation, 9,43 we investigated here inflammatory markers. Previous data have shown NF‐κB activation in BV‐2 cells 44 following IH treatments. Moreover, in non‐microglial cells, it has been demonstrated that the NF‐κB pathway is strongly triggered by IH conditions.…”

Section: Discussionmentioning

confidence: 86%

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Intermittent hypoxia treatments cause cellular priming in human microglia

Felice

Germelli

Piccarducci

et al. 2023

J Cellular Molecular Medi

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Obstructive sleep apnoea syndrome (OSAS) is a sleep-disordered breathing, often preceding dementia and cognitive impairment. 1 Specifically, sleep disturbance has been associated with cognitive dysfunctions, deficits in vigilance, memory and visuo-spatial abilities, 2 with particular regard to mild cognitive impairment (MCI) onset. 3,4 However, the exact mechanisms by which these pathologies are related to OSAS remain to be elucidated.OSAS is characterized by recurrent episodes of intermittent hypoxia (IH), 5,6 leading to cyclic oscillations of oxygen levels (pO 2 ) in arterial blood and tissues as well as establishing chronic hypoxia/

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 86%

Intermittent hypoxia treatments cause cellular priming in human microglia

Felice

Germelli

Piccarducci

et al. 2023

J Cellular Molecular Medi

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“…Moreover, our previous study revealed that the overexpression of SENP1 could inhibit the in ammatory responses induced by CIH in vitro and in vivo [40]. Thus, SENP1 mediated in ammatory response may be involved in CIH-associated hippocampal injuries.…”

Section: Discussionmentioning

confidence: 93%

SENP1 modulates chronic intermittent hypoxia-induced neuroinflammation and neuronal injury by inhibiting microglial migration via the de-SUMOylation of TOM1

Wang

et al. 2022

Preprint

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Chronic intermittent hypoxia (CIH), a prominent characteristic of obstructive sleep apnea syndrome, accelerates OSAS-associated neurocognitive impairment by initiating neuroinflammation. Microglia play a vital role in neuronal development and detrimental phagocytosis through migration. SUMO-specific proteases 1 (SENP1) has been implicated in cells migration. However, the role of SENP1 in the progression of CIH-induced neuroinflammation of microglia remains unknown. We aimed to investigate the effect of SENP1 on microglial migration, neuroinflammation, neuronal injury and Aβ deposition after the CIH insult. The CIH model was established using an intermittent hypoxia device. SENP1 overexpression and knockdown were induced in vitro and in vivo, respectively. Results showed that CIH downregulated the expression of both SENP1 and TOM1, enhanced the SUMOylation of TOM1, and promoted microglial migration, neuroinflammation, neuronal apoptosis and neuronal Aβ42 deposition in vitro and in vivo. After SENP1 overexpression in vitro, the enhanced SUMOylation of TOM1 was inhibited; the expression of TOM1 and microglial migration were enhanced; neuroinflammation, neuronal apoptosis and neuronal accumulation of Aβ42 by CIH was significantly reduced. However, the administration of siRNA-TOM1 abolished the microglial migration, neuroinflammation, neuronal apoptosis and reduction of Aβ42 deposition. After SENP1 knockdown in vivo, the SUMOylation enhancement of TOM1 was accelerated, microglial migration was inhibited. Neuroinflammation, neuronal apoptosis, neuronal Aβ42 deposition, cognitive impairment was significantly aggrandized. Overall, the results demonstrated that SENP1 promoted microglial migration by regulating the de-SUMOylation of TOM1, thus contributing to neuroinflammation, neuronal apoptosis and the clearance of Aβ42 deposition induced by CIH injury.

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“…In the present study, LPS reduced the expression of Foxc1 in microglial BV-2 cells, whilst CLP surgery also downregulated the expression of Foxc1 in the hippocampus of mice compared with their corresponding control groups. Foxc1 contains a common 100-amino acid winged-helix DNA-binding domain that serves key roles in cell proliferation, differentiation migration and survival ( 19 , 33 ). A previous study showed that Foxc1 promoted the migration of hepatocellular carcinoma (HCC) cells, as knockdown of Foxc1 inhibited the migration of HCC cells ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway

Wang

Song

et al. 2022

Mol Med Rep

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Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. The cognitive dysfunction that ensues during SAE has been reported to be caused by impairments of the hippocampus. Microglia serves a key role in neuroinflammation during SAE through migration. Forkhead box C1 (Foxc1) is a member of the forkhead transcription factor family that has been found to regulate in cell migration. However, the role of Foxc1 in neuroinflammation during SAE remains unknown. In the present study, the mechanistic role of Foxc1 on microglial migration, neuroinflammation and neuronal apoptosis during the occurrence of cognitive dysfunction in SAE was investigated. A microglia-mediated inflammation model was induced by LPS in BV-2 microglial cells in vitro , whilst a SAE-related cognitive impairment model was established in mice using cecal ligation and perforation (CLP) surgery. Cognitive function in mice was evaluated using the Morris Water Maze (MWM) trial. Lipopolysaccharide (LPS) treatment was found to trigger BV-2 cell migration, inflammation and neuronal apoptosis. In addition, CLP surgery induced cognitive injury, which was indicated by longer latencies and shorter dwell times in the goal quadrant compared with those in the Sham group in the MWM trial. LPS treatment or CLP induction decreased the expression of Foxc1 and inhibitor of NF-κB (IκΒα) whilst increasing that of p65, IL-1β and TNF-α. After Foxc1 was overexpressed, the cognitive dysfunction of mice that underwent CLP surgery was improved, with the expression of IκBα also increased, microglial cell migration, the expression of p65, IL-1β and TNF-α and neuronal apoptosis were all decreased in vivo and in vitro , which were in turn reversed by the inhibition of IκBα in vitro . Overall, these results suggest that the overexpression of Foxc1 inhibited microglial migration whilst suppressing the inflammatory response and neuronal apoptosis by regulating the IκBα/NF-κB pathway, thereby improving cognitive dysfunction during SAE.

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SENP1 modulates microglia‐mediated neuroinflammation toward intermittent hypoxia‐induced cognitive decline through the de‐SUMOylation of NEMO

Cited by 12 publications

References 52 publications

Intermittent hypoxia treatments cause cellular priming in human microglia

Intermittent hypoxia treatments cause cellular priming in human microglia

SENP1 modulates chronic intermittent hypoxia-induced neuroinflammation and neuronal injury by inhibiting microglial migration via the de-SUMOylation of TOM1

Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway

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