Extracellular vesicles in type 2 diabetes mellitus: key roles in pathogenesis, complications, and therapy

Xiao, Yongshun; Zheng, Lei; Zou, Xiaofeng; Wang, Jigang; Zhong, Jianing; Zhong, Tianyu

doi:10.1080/20013078.2019.1625677

Cited by 100 publications

(93 citation statements)

References 112 publications

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“…5 ). As is well-known, the biological functions of exosomes were determined by the loaded biological components and information, including growth factors, proteins, DNA, long non-coding RNAs and, in particularly, miRNAs [ 9 , [58] , [59] , [60] , [61] ]. MiRNAs, small non-coding RNAs of 18–25 nucleotides, could suppress gene expression to control various biological processes, including cell survival, cell apoptosis, cell cycle and gene regulation in cells [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

2021

Bioactive Materials

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Recently, exosomes have been extensively applied in tissue regeneration. However, their practical applications are severely restricted by the limited exosome secretion capability of cells. Therefore, developing strategies to enhance the production of exosomes and improve their biological function attracts great interest. Studies have shown that biomaterials can significantly enhance the paracrine effects of cells and exosomes are the main signal carriers of intercellular paracrine communication, thus biomaterials are considered to affect the exosome secretion of cells and their biological function. In this study, a widely recognized biomaterial, 45S5 Bioglass® (BG), is used to create a mild and cell-friendly microenvironment for mesenchymal stem cells (MSCs) with its ion products. Results showed that BG ion products can significantly improve exosome production of MSCs by upregulating the expression of neutral sphingomyelinase-2 (nSMase2) and Rab27a which enhanced the nSMases and Rab GTPases pathways, respectively. Besides, microRNA analysis indicates that BG ion products can modulate the cargoes of MSCs-derived exosomes by decreasing microRNA-342-5p level while increasing microRNA-1290 level. Subsequently, the function of exosomes is modified as their capabilities of promoting the vascularization of endothelial cells and facilitating the intradermal angiogenesis are enhanced. Taken together, BG ion products are confirmed to enhance exosome production and simultaneously improve exosome function, suggesting a feasible approach to improve the practical application of exosomes in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

2021

Bioactive Materials

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“…Several studies suggest an important role of abnormal EV in the etiology of diabetes mellitus and related cardiovascular disease [ 1 , 46 , 56 , 73 , 74 ].…”

Section: Ev and Metabolic Syndromementioning

confidence: 99%

Extracellular Vesicles in Comorbidities Associated with Ischaemic Heart Disease: Focus on Sex, an Overlooked Factor

Penna

Femminò

Alloatti

et al. 2021

JCM

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Extracellular vesicles (EV) are emerging early markers of myocardial damage and key mediators of cardioprotection. Therefore, EV are becoming fascinating tools to prevent cardiovascular disease and feasible weapons to limit ischaemia/reperfusion injury. It is well known that metabolic syndrome negatively affects vascular and endothelial function, thus creating predisposition to ischemic diseases. Additionally, sex is known to significantly impact myocardial injury and cardioprotection. Therefore, actions able to reduce risk factors related to comorbidities in ischaemic diseases are required to prevent maladaptive ventricular remodelling, preserve cardiac function, and prevent the onset of heart failure. This implies that early diagnosis and personalised medicine, also related to sex differences, are mandatory for primary or secondary prevention. Here, we report the contribution of EV as biomarkers and/or therapeutic tools in comorbidities predisposing to cardiac ischaemic disease. Whenever possible, attention is dedicated to data linking EV to sex differences.

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“…Mitochondrial stress is characterized by the 2 Mediators of Inflammation accumulation of unfolded proteins which ultimately lead to impaired mitochondrial function [33]. It is evident that hyperglycemia-induced alternations in mitochondrial electron transport are a key causative factor for mitochondrial dysfunction [34]. Molecular stress proteins are a group of proteins which enable mitochondria to respond to stressinduced protein misfolding [35].…”

Section: Role Of Molecular Stress Proteins During Mitochondrialmentioning

confidence: 99%

“…The most recent studies have focused considerable attention on the role of exosomes and pathogenesis of diabetes. It is becoming evident that exosomes are involved in the pathogenesis of diabetic complications through stimulating inflammation, lowering GLUT4 as well as insulin receptors [34]. Interestingly, these exosomes can transport abnormal molecules and microRNA in diabetic patients.…”

Section: Neuron-astrocyte Communication Throughmentioning

confidence: 99%

Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation

Liyanagamage

Martinus

2020

Mediators of Inflammation

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Diabetes mellitus is the most common metabolic disorder characterized by hyperglycemia and associated malfunctions of the metabolism of carbohydrates, proteins, and lipids. There is increasing evidence of a relationship between diabetes and vascular dementia. Interestingly, hyperglycemia-linked neuroinflammation in the central nervous system is considered to play a key role during vascular dementia in diabetic patients. However, the mechanisms responsible for the relationship between hyperglycemia and neuroinflammation is not clearly understood. Diabetes-induced alternations in the blood-brain barrier permit high glucose influx into the brain cells via glucose transporters and promote oxidative stress through overproduction of reactive oxygen species. Despite many studies demonstrating a link between oxidative stress and mitochondrial dysfunction, the relationship between mitochondrial dysfunction and neuron inflammation during hyperglycemia remains to be established. In this review, we will focus on diabetes-induced changes in the central nervous system and the role of mitochondrial heat shock protein 60 (HSP60) as an initiator of oxidative stress and potential modulator of neuroinflammation. We suggest that oxidative stress-mediated mitochondrial dysfunction stimulates the upregulation of mitochondrial heat shock protein 60 (HSP60) and ultimately initiates inflammatory pathways by activating pattern recognition receptors. HSP60 also could be a focal point in the development of a biomarker of neuroinflammation as HSP60 is known to be significantly elevated in diabetic patients. Interestingly, extracellular secretion of HSP60 via exosomes suggests that inflammation could spread to neighboring astrocytes by activating pattern recognition receptors of astrocytes via neuronal exosomes containing HSP60. A mechanism for linking neuron and astrocyte inflammation will provide new therapeutic approaches to modulate neuroinflammation and therefore potentially ameliorate the cognitive impairment in diabetic brains associated with vascular dementia.

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Extracellular vesicles in type 2 diabetes mellitus: key roles in pathogenesis, complications, and therapy

Cited by 100 publications

References 112 publications

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

Extracellular Vesicles in Comorbidities Associated with Ischaemic Heart Disease: Focus on Sex, an Overlooked Factor

Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation

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