Astrocyte-Derived Extracellular Vesicle–Mediated Activation of Primary Ciliary Signaling Contributes to the Development of Morphine Tolerance

Ma, Rong; Kutchy, Naseer A.; Hu, Guoku

doi:10.1016/j.biopsych.2021.06.009

Cited by 24 publications

(20 citation statements)

References 68 publications

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“…It is thus possible that EVs could play a crucial role in aging and age-related diseases via mediating the activation of ciliary signaling pathways. Moreover, as reported recently, EVs, primary cilia and ciliary signaling could also be involved in intercellular communication ( Ma et al, 2021 ). The underlying mechanism(s) of EV-mediated ciliary signaling in brain disorders warrants further investigation.…”

Section: Discussionmentioning

confidence: 56%

Primary cilia and ciliary signaling pathways in aging and age-related brain disorders

Kutchy

Chen

et al. 2022

Neurobiology of Disease

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Section: Discussionmentioning

confidence: 56%

Primary cilia and ciliary signaling pathways in aging and age-related brain disorders

Kutchy

Chen

et al. 2022

Neurobiology of Disease

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“…Notably, the morphine addiction pathway was also ranked in the top 30 enriched pathways among therapyresistant and -reversed lncRNA-correlating genes (Supplemental Figures 2A and 2B). This result suggests that the use of morphine could dysregulate the expression of lncRNAs, and in turn, affect morphine tolerance and addiction cellular signaling pathways [24,25]. As shown in Figure 5(a), the expressions of most cell-cycle genes were shown to be positively correlated with the expression of SNHG1, with the strongest correlation between SNHG1 and MAD2L1 -a positive regulator of cell proliferation [26,27].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 88%

Therapy-resistant and -sensitive lncRNAs, SNHG1 and UBL7-AS1 promote glioblastoma cell proliferation

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

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The current treatment options for glioblastoma (GBM) can result in median survival of 15-16 months only, suggesting the existence of therapy-resistant factors. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play an essential role in the development of various brain tumors, including GBM. This study aimed to identify therapy-resistant and therapy-sensitive GBM associated lncRNAs and their role in GBM. We conducted a genome-wide transcriptional survey to explore the lncRNA landscape in 195 GBM brain tissues. Cell proliferation was evaluated by CyQuant assay and Ki67 immunostaining. Expression of MAD2L1 and CCNB2 was analyzed by western blotting. We identified 51 lncRNAs aberrantly expressed in GBM specimens compared with either normal brain samples or epilepsy non-tumor brain samples. Among them, 27 lncRNAs were identified as therapy-resistant lncRNAs that remained dysregulated after both radiotherapy and chemoradiotherapy; while 21 lncRNAs were identified as therapy-sensitive lncRNAs whose expressions were reversed by both radiotherapy and chemoradiotherapy. We further investigated the potential functions of the therapy-resistant and therapy-sensitive lncRNAs and demonstrated their relevance to cell proliferation. We also found that the expressions of several lncRNAs, including SNHG1 and UBL7-AS1, were positively correlated with cell-cycle genes’ expressions. Finally, we experimentally confirmed the function of a therapy-resistant lncRNA, SNHG1, and a therapy-sensitive lncRNA, UBL7-AS1, in promoting cell proliferation in GBM U138MG cells. Our in vitro results demonstrated that knockdown of SNHG1 and UBL7-AS1 showed an additive effect in reducing cell proliferation in U138MG cells.

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“…EVs have a pivotal role in intercellular communication under normal and diseased conditions ( Patters and Kumar, 2018 ; Ma et al, 2021 ). Moreover, EVs have tremendous potential to be used as delivery vehicles for therapeutics as they can cross the BBB ( Alvarez-Erviti et al, 2011 ; Yang et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…The EV and EV devoid supernatant samples were resuspended in the protein lysis buffer to detect EV markers—Alix, TSG101, and CD63—by Western blotting. The EV number and size distribution were analyzed using a ZetaView Particle Metrix, as previously reported ( Ma et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain

Kutchy

Liu

et al. 2022

Front. Pharmacol.

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Extracellular vesicles (EVs) are small lipid membrane-bound vesicles that can pass the blood–brain barrier. Therefore, EVs could be used for the delivery of therapeutics to the brain. Herein, we investigated the biodistribution of intranasal perfusion of ultrasmall superparamagnetic iron oxide (USPIO)-labeled astrocyte-derived EVs (ADEVs) in mice. We used Western blotting, transmission electron microscopy (TEM), and nanoparticle uptake assay to characterize ADEVs. In addition, intranasal perfusion coupled with magnetic resonance imaging (MRI) was employed to determine the distribution of USPIO-labeled ADEVs in mice. Our results showed the uptake of USPIO by mouse astrocytes and ADEVs. In addition, we confirmed the biodistribution of ADEVs in the brain and other internal organs, including the kidneys, liver, and spleen. Our results suggest that USPIO did not affect mouse astrocyte cell survivability and EV release. Therefore, intranasal delivery of therapeutic loaded EVs could be used for the treatment of various brain disorders.

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Astrocyte-Derived Extracellular Vesicle–Mediated Activation of Primary Ciliary Signaling Contributes to the Development of Morphine Tolerance

Cited by 24 publications

References 68 publications

Primary cilia and ciliary signaling pathways in aging and age-related brain disorders

Primary cilia and ciliary signaling pathways in aging and age-related brain disorders

Therapy-resistant and -sensitive lncRNAs, SNHG1 and UBL7-AS1 promote glioblastoma cell proliferation

Extracellular Vesicle-Mediated Delivery of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles to Mice Brain

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