Insulin‑like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway

Zhang, Duo; Yuan, Yuan; Zhu, Jichao; Zhu, Di; Li, Chenxi; Cui, Wei; Wang, Lei; Ma, Song; Duan, Shuo; Liu, Baoge

doi:10.3892/etm.2021.10700

Cited by 26 publications

(14 citation statements)

References 77 publications

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“…This might suggest that Igf1 had a long‐term effect on promoting angiogenesis after SCI. Igf1 is a cytokine that participates in neural development and injury repair, which can decrease EC apoptosis and microvascular damage, alleviate neuropathic pain, and promote neurological functional recovery after SCI 54–56 . It is required for vessel remodeling and has a neuroprotective effect on the CNS 57,58 .…”

Section: Discussionmentioning

confidence: 99%

Single‐cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury

et al. 2022

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Spinal cord injury (SCI) results in dynamic alterations of the microenvironment at the lesion site, which inevitably leads to neuronal degeneration and functional impairment. The destruction of the spinal vascular system leads to a significant deterioration of the milieu, which exacerbates inflammatory response and deprives cells of nutrient support in the lesion. Limited endogenous angiogenesis occurs after SCI, but the cellular events at the lesion site during this process are unclear so far. Here, we performed single‐cell RNA sequencing (scRNA‐seq) on spinal cord tissues of rats at different time points after SCI. After clustering and cell‐type identification, we focused on vascular endothelial cells (ECs), which play a pivotal role in angiogenesis, and drew the cellular and molecular atlas for angiogenesis after SCI. We found that microglia and macrophages promote endogenous angiogenesis by regulating EC subsets through SPP1 and IGF signaling pathways. Our results indicate that immune cells promote angiogenesis by regulating specific subsets of vascular ECs, which provides new clues for exploring SCI intervention.

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Section: Discussionmentioning

confidence: 99%

Single‐cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury

et al. 2022

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“…Moderate activation of autophagy promotes cell survival, whereas excessive activation leads to cell death. Autophagy is a dynamic process that has positive or negative effects, depending on its timing 113 . The promotion of autophagy immediately after ischemic SCI promotes the recovery of motor function, while the inhibition of autophagy has the opposite effect; inhibition of autophagy at 48 h after SCI increases the recovery of motor function, while stimulation of autophagy has no effect 114 .…”

Section: Inflammation Cell Death and Glial Scar Formation In Secondar...mentioning

confidence: 99%

“…Autophagy is a dynamic process that has positive or negative effects, depending on its timing. 113 The promotion of autophagy immediately after ischemic SCI promotes the recovery of motor function, while the inhibition of autophagy has the opposite effect; inhibition of autophagy at 48 h after SCI increases the recovery of motor function, while stimulation of autophagy has no effect. 114 Therefore, autophagy at an early stage (i.e., immediately after injury) after SCI inhibits apoptosis and inflammation; however, excessive autophagy at a later stage (i.e., 48 h after injury) aggravates the injury by inducing autophagic cell death.…”

Section: Cell Deathmentioning

confidence: 99%

“…Intravenous injection of IGF‐I in SCI rats causes PI3K/AKT/mTOR activation, upregulation of the expression levels of p‐AKT and p‐mTOR, and LC3II inhibition. In addition, IGF‐I injection weakens the activation of caspase‐9, increases the expression of the anti‐apoptotic protein Bcl2, inhibits apoptosis and excessive autophagy after SCI, and promotes the recovery of nerve function 113,230 …”

Section: Regulation Of Pi3k/akt Signalling Pathway In Spinal Cord Injurymentioning

confidence: 99%

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ThePI3K/AKTsignalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

et al. 2022

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Objects: Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine-threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI.Materials and Methods: By searching articles related to the TSCI field and the PI3K/AKT signaling pathway, we summarized the mechanisms of secondary TSCI and the PI3K/AKT signaling pathway; we also discuss current and potential future treatment methods for TSCI based on the PI3K/AKT signaling pathway.Results: Early apoptosis and autophagy after TSCI protect the body against injury; a prolonged inflammatory response leads to the accumulation of pro-inflammatory factors and excessive apoptosis, as well as excessive autophagy in the surrounding normal nerve cells, thus aggravating TSCI in the subacute stage of secondary injury. Initial glial scar formation in the subacute phase is a protective mechanism for TSCI, which limits the spread of damage and inflammation. However, mature scar tissue in the chronic phase hinders axon regeneration and prevents the recovery of nerve function. Activation of PI3K/AKT signaling pathway can inhibit the inflammatory response and apoptosis in the subacute phase after secondary TSCI; inhibiting this pathway in the chronic phase can reduce the formation of glial scar. Conclusion:The PI3K/AKT signaling pathway has an important role in the recovery of spinal cord function after secondary injury. Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury and inhibiting this pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.Xuegang He, Ying Li and Bo Deng contributed equally to this study.

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“…The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the most important signaling pathways with a critical biological function in various diseases [ 60 , 61 ], including neurological disorders [ 62 ]. As reported, numerous drugs exert their neuroprotective effect via the PI3K/Akt/mTOR signaling pathway [ 63 ].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy

Zhao

Wu²,

Lin

et al. 2022

Cell Mol Biol Lett

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Vital organ injury is one of the leading causes of global deaths. Accumulating studies have demonstrated that dexmedetomidine (DEX) has an outstanding protective effect on multiple organs for its antiinflammatory and antiapoptotic properties, while the underlying molecular mechanism is not clearly understood. Autophagy, an adaptive catabolic process, has been found to play a crucial role in the organ-protective effects of DEX. Herein, we present a first attempt to summarize all the evidence on the proposed roles of autophagy in the action of DEX protecting against vital organ injuries via a comprehensive review. We found that most of the relevant studies (17/24, 71%) demonstrated that the modulation of autophagy was inhibited under the treatment of DEX on vital organ injuries (e.g. brain, heart, kidney, and lung), but several studies suggested that the level of autophagy was dramatically increased after administration of DEX. Albeit not fully elucidated, the underlying mechanisms governing the roles of autophagy involve the antiapoptotic properties, inhibiting inflammatory response, removing damaged mitochondria, and reducing oxidative stress, which might be facilitated by the interaction with multiple associated genes (i.e., hypoxia inducible factor-1α, p62, caspase-3, heat shock 70 kDa protein, and microRNAs) and signaling cascades (i.e., mammalian target of rapamycin, nuclear factor-kappa B, and c-Jun N-terminal kinases pathway). The authors conclude that DEX hints at a promising strategy in the management of vital organ injuries, while autophagy is crucially involved in the protective effect of DEX.

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Insulin‑like growth factor 1 promotes neurological functional recovery after spinal cord injury through inhibition of autophagy via the PI3K/Akt/mTOR signaling pathway

Cited by 26 publications

References 77 publications

Single‐cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury

Single‐cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury

ThePI3K/AKTsignalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy

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