SENP1 modulates chronic intermittent hypoxia-induced inflammation of microglia and neuronal injury by inhibiting TOM1 pathway.

Hongwei Wang, Xu Wang, Yubin Shen, Yanmin Wang, Tianyun Yang, Jinyuan Sun, Song Liu

International immunopharmacology 2023 Jun

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Chronic intermittent hypoxia (CIH) is a characteristic pathophysiological change of obstructive sleep apnea syndrome (OSAS). Inflammation of microglia induced by CIH, plays a vital role in OSAS-associated cognitive dysfunction. SUMO-specific proteases 1 (SENP1) has been implicated in tumor inflammatory microenvironment and cells migration. However, the role of SENP1 in CIH-induced neuroinflammation remains unknown. We aimed to investigate the effect of SENP1 on neuroinflammation and neuronal injury. After the preparation of SENP1 overexpression microglia and SENP1 knockout mouse, CIH microglia and mice were established using an intermittent hypoxia device. Results showed that CIH reduced the level of SENP1 and TOM1, induced the SUMOylation of TOM1, and promoted microglial migration, neuroinflammation, neuronal amyloid-beta 42 (Aβ42) deposition and apoptosis in vitro and in vivo. After SENP1 overexpression in vitro, the enhanced SUMOylation of TOM1 was inhibited; the level of TOM1 and microglial migration were enhanced; neuroinflammation, neuronal Aβ42 deposition and apoptosis were significantly reduced. However, the administration of siRNA-TOM1 suppressed microglial migration, neuroinflammation, neuronal Aβ42 deposition and apoptosis. After SENP1 knockout in vivo, the SUMOylation enhancement of TOM1 was accelerated, microglial migration was inhibited. Neuroinflammation, neuronal Aβ42 deposition and apoptosis, cognitive impairment was significantly exacerbated. Overall, the results demonstrated that SENP1 promoted microglial migration by alleviating the de-SUMOylation of TOM1, thus contributing to attenuate neuroinflammation, neuronal Aβ42 deposition and neuronal apoptosis induced by CIH. Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Hongwei Wang, Xu Wang, Yubin Shen, Yanmin Wang, Tianyun Yang, Jinyuan Sun, Song Liu. SENP1 modulates chronic intermittent hypoxia-induced inflammation of microglia and neuronal injury by inhibiting TOM1 pathway. International immunopharmacology. 2023 Jun;119:110230