Olfactory Mucosa Mesenchymal Stem Cells Ameliorate Cerebral Ischemic/Reperfusion Injury Through Modulation of UBIAD1 Expression

Liu, Jianyang; Huang, Yan; He, Jialin; Zhuo, Yi; Chen, Wei; Ge, Lite; Duan, Da; Lu, Ming

doi:10.3389/fncel.2020.580206

Cited by 18 publications

(14 citation statements)

References 70 publications

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“…Previously, we discovered that UBIAD1 exhibits multi-subcellular organelles colocalization in mouse N2A neuroblastoma cells, including in the mitochondria, endoplasmic reticulum, and Golgi apparatus 26 . Up-regulating the expression of UBIAD1 could attenuated cerebral ischemia/reperfusion-induced mitochondrial fragmentation and dysfunction 38 , and ameliorated the fragmentation and reduced the level of oxidative stress-related protein expression in both the endoplasmic reticulum and Golgi apparatus.…”

Section: Discussionmentioning

confidence: 95%

L-3-n-butylphthalide promotes restoration after an experimental animal model of intracerebral hemorrhage

Jianyang

Xiao

2021

Int. J. Med. Sci.

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Intracerebral hemorrhage (ICH) is a devastating type of stroke with high morbidity and mortality, and the effective therapies for ICH remain to be explored. L-3-n-butylphthalide (NBP) is widely used in the treatment of ischemic stroke. However, few studies evaluated the therapeutic effects of NBP on ICH. Therefore, the present study aims to evaluate the effects of NBP on ICH and its potential mechanism. The rats were randomly divided into sham-operated group, saline-treated (ICH + saline) group, and NBP-treated (ICH + NBP) group. The ICH model of SD rats induced by IV collagenase was established. The modified Garcia JH score was used to detect the neurological deficit in rats. Western Blot and immunohistochemistry analysis was applied to test the levels of UBIAD1 and caspase-3 expressions in the perihematomal region. The rates of apoptotic cells were detected by TUNEL staining. The results showed that NBP up-regulated the expression of UBIAD1, reduced the apoptotic cells in the perihematomal region, and improved the neurological deficit. Taken together, our study added some new evidence to the application of NBP in ICH treatment.

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Section: Discussionmentioning

confidence: 95%

L-3-n-butylphthalide promotes restoration after an experimental animal model of intracerebral hemorrhage

Jianyang

Xiao

2021

Int. J. Med. Sci.

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“…Although we suggested that hypoxic OM-MSCs inhibited microglial pyroptosis in ICH, the specific mechanism of the inflammatory response of microglia regulated by hypoxic OM-MSCs after ICH injury is still unclear. Previously, we demonstrated that OM-MSCs exerts neuroprotective effects on cerebral ischemia/reperfusion injury (47,48,50). We also revealed that hypoxia-preconditioned OM-MSCs inhibit pyroptotic death of microglial cells by activating the hypoxia inducible factor-1α (HIF-1α) in vitro model of ischemic stroke (49).…”

Section: Effects Of Mscs On Microglial Pyroptosis Post-ichmentioning

confidence: 97%

“…Olfactory mucosa MSCs (OM-MSCs) localized in the nasal lamina propria have recently been recognized as an ideal source of MSCs, as they are easily accessible and situated for autologous transplantation (46). Previously, we demonstrated that OM-MSCs exerts neuroprotective effects in ischemic stroke (47,48). We also revealed that hypoxia-preconditioned OM-MSCs inhibited microglial pyroptosis in an in vitro model (49) and affirmed that hypoxic preconditioning enhanced the therapeutic efficacy of OM-MSCs in an in vivo model (50).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-preconditioned mesenchymal stem cells attenuate microglial pyroptosis after intracerebral hemorrhage

Liu¹,

He²,

Huang³

et al. 2021

Ann Transl Med

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Background: Microglia plays a vital role in neuroinflammation, contributing to the pathogenesis of intracerebral hemorrhage (ICH)-induced brain injury. Mesenchymal stem cells (MSCs) hold great potential for treating ICH. We previously revealed that MSCs ameliorate the microglial pyroptosis caused by an ischemic stroke. However, whether MSCs can modulate microglial pyroptosis after ICH remains unknown.This study aimed to investigate the neuroprotective effects of hypoxia-preconditioned olfactory mucosa MSCs (OM-MSCs) on ICH and the possible mechanisms.Methods: ICH was induced in mice via administration of collagenase IV. At 6 h post-ICH, 2-4×10 5 normoxic/hypoxic OM-MSCs or saline were intracerebrally administered. To evaluate the neuroprotective effects, the behavioral outcome, apoptosis, and neuronal injury were measured. Microglia activation and proinflammatory cytokines were applied to detect neuroinflammation. Microglial pyroptosis was determined by western blotting, immunofluorescence staining, and transmission electron microscopy (TEM). Results:The two OM-MSC-transplanted groups exhibited significantly improved functional recovery and reduced neuronal injury, especially the hypoxic OM-MSCs group. Hypoxic OM-MSCs attenuated microglial activation as well as the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Moreover, we found that hypoxia-preconditioned OM-MSCs ameliorated pyroptosis by diminishing the levels of pyroptosis-associated proteins in peri-hematoma brain tissues, decreasing the expression of the microglial nod-like receptor family protein 3 (NLRP3) and caspase-1, and reducing the membrane pores on microglia post-ICH.Conclusions: Our study showed that hypoxic preconditioning augments the therapeutic efficacy of OM-MSCs, and hypoxia-preconditioned OM-MSCs alleviate microglial pyroptosis in the ICH model.

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“…Li et al (2012a) have found that adipose-derived mesenchymal stem cells (ADMSCs) attenuated cerebral ischemia-reperfusion injury through suppressing iNOS. Another two interesting findings indicated that olfactory mucosa mesenchymal stem cells (OM-MSCs) exert neuroprotective effects by rescuing the function of mitochondria and Golgi apparatus and enhancing antioxidation via upregulation of UBIAD1 and SPCA1 (He et al, 2020;Liu et al, 2020b). Moreover, that MSCs modified with diverse molecules exhibited antioxidative stress effects on ischemic stroke models have also been reported, such as C-C motif chemokine receptor 2 (CCR-2), brain-derived neurotrophic factor (BDNF), and circRNA-Akap7 (Lu et al, 2016;Huang et al, 2018b;Xu et al, 2020).…”

Section: Mscs Inhibit the Production Of Ros And Rnsmentioning

confidence: 99%

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Liu

Huang

et al. 2021

Front. Neurosci.

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Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic stroke are to restore blood flow, which reduce disability but are time limited. The interruption of blood flow in ischemic stroke contributes to intricate pathophysiological processes. Oxidative stress and inflammatory activity are two early events in the cascade of cerebral ischemic injury. These two factors are reciprocal causation and directly trigger the development of autophagy. Appropriate autophagy activity contributes to brain recovery by reducing oxidative stress and inflammatory activity, while autophagy dysfunction aggravates cerebral injury. Abundant evidence demonstrates the beneficial impact of mesenchymal stem cells (MSCs) and secretome on cerebral ischemic injury. MSCs reduce oxidative stress through suppressing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and transferring healthy mitochondria to damaged cells. Meanwhile, MSCs exert anti-inflammation properties by the production of cytokines and extracellular vesicles, inhibiting proinflammatory cytokines and inflammatory cells activation, suppressing pyroptosis, and alleviating blood–brain barrier leakage. Additionally, MSCs regulation of autophagy imbalances gives rise to neuroprotection against cerebral ischemic injury. Altogether, MSCs have been a promising candidate for the treatment of ischemic stroke due to their pleiotropic effect.

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Olfactory Mucosa Mesenchymal Stem Cells Ameliorate Cerebral Ischemic/Reperfusion Injury Through Modulation of UBIAD1 Expression

Cited by 18 publications

References 70 publications

L-3-n-butylphthalide promotes restoration after an experimental animal model of intracerebral hemorrhage

L-3-n-butylphthalide promotes restoration after an experimental animal model of intracerebral hemorrhage

Hypoxia-preconditioned mesenchymal stem cells attenuate microglial pyroptosis after intracerebral hemorrhage

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

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