Ginsenoside Rg1-induced activation of astrocytes promotes functional recovery via the PI3K/Akt signaling pathway following spinal cord injury

Life Sciences ◽  
2020 ◽  
Vol 252 ◽  
pp. 117642
Author(s):  
Long Xu ◽  
Yin-Yao Tang ◽  
Xing-Lei Ben ◽  
Mao-Hua Cheng ◽  
Wei-Xiao Guo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Akt Signaling ◽  
Ginsenoside Rg1 ◽  
Akt Signaling Pathway ◽  
Cord Injury

scholarly journals Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

2020 ◽  
Author(s):  
Xu Yan ◽  
Yong Cao ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Umbilical Vein ◽  
Motor Evoked Potential ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Cord Injury

Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

2020 ◽  
Author(s):  
Yong Cao ◽  
Xu Yan ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Tube Formation ◽  
Akt Signaling Pathway ◽  
Functional Studies ◽  
Cord Injury

Abstract Background: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate the effect of an administered injection of exosomes derived human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism.Methods: Exosome were isolate from USC and identified by transmission electron Microscopy (TEM) and western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model was assessed.Results: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in (USC-Exo) and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

Interference of interleukin-1β mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Yi-li Wang ◽  
Xi Hu ◽  
Qin-xuan Li ◽  
Li-xin Zhang ◽  
Qing-jie Xia ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Motor Function ◽  
Akt Signaling ◽  
Inflammatory Factors ◽  
Akt Signaling Pathway ◽  
Cord Injury ◽  
Spinal Cord Contusion ◽  
Recovery Of Motor Function

Abstract Background: Spinal cord contusion (SCC) results in a series of pathophysiologic consequences such as edema, apoptosis, and inflammation. However, inflammation may also be beneficial for the recovery of motor function after SCC, but the underlying mechanisms remain incompletely elucidated. Interleukin-1 beta (IL-1β) is a pro-inflammatory factor that has synergistic effects with other inflammatory factors to aggravate spinal cord injury. Inflammatory factors have been found to activate the serine/threonine-specific protein kinase, protein kinase B (AKT) and to inhibit cell survival, but it is not clear whether inflammation upregulates the expression of IL-1β in the rat model of SCC and subsequently interferes in the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway. Therefore, this study explored whether IL-1β affects the recovery of motor function in spinal cord injury by interfering with the PI3K/AKT signaling pathway. Method: SCC rats were established by the Allen method. The Basso Beattie Bresnahan (BBB) scoring was used to assess motor function in the spinal cord of injured rats. Quantitative polymerase chain reaction and Western blot were used to determine the expression of genes and proteins of IL-1β, PI3K, and AKT1. Immunohistochemistry and immunofluorescence were used to locate and detect IL-1β and AKT1 proteins in spinal cord tissue. To further explore the underlying mechanism of IL-1β, lentivirus was constructed by RNA interfering (RNAi) technique to inhibit the expression of IL-1β, and bioinformatics was applied to show the relationship between IL-1β and AKT1. Results: BBB scores decreased after SCC, and IL-1β and AKT1 was located in the cytoplasm of spinal cord anterior horn neurons. In the early stage of SCC, the expression level of IL-1β gene and protein in the experimental group was higher than that in the sham operated group. At the same time, expression of the AKT1 gene decreased. After expression of IL-1β mediated by lentivirus was inhibited, BBB scores increased significantly, and spinal cord motor function improved. Bioinformatic analysis revealed a relationship between IL-1β and AKT1. In addition, AKT1 gene expression was upregulated and PI3K expression was unchanged in the PI3K/AKT signaling pathway. Conclusion IL-1β not only exacerbates the inflammatory response after SCC, but also interferes with motor function. Inhibition of IL-1β may promote recovery of spinal cord injury by upregulating AKT1 in the PI3K/AKT signaling pathway, which provides a new perspective for future clinical practice in treating spinal cord injury

scholarly journals Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong Cao ◽  
Yan Xu ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Tube Formation ◽  
Akt Signaling Pathway ◽  
Functional Studies ◽  
Cord Injury

Abstract Background Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate if the effect of an administered injection of exosomes derived from human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism. Methods Exosomes were isolated from USC and identified by transmission electron microscopy (TEM) and Western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model were assessed. Results In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood-brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in USC-Exo and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dayu Pan ◽  
Yongjin Li ◽  
Fuhan Yang ◽  
Zenghui Lv ◽  
Shibo Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Schwann Cell ◽  
Western Blot ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Cord Injury ◽  
Toll Like Receptor 2

Abstract Background Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood–brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. Methods A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and β-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2−/−). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKβ inhibitor SC-514 was used to validate the involved signaling pathway. Results Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKβ inhibitor SC-514 was also used to validate this signaling pathway. Conclusion Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

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