Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM

Xu, Shihao; Cheuk, Yin Celeste; Jia, Yichen; Tian, Chen; Chen, Juntao; Luo, Yongsheng; Cao, Yirui; Guo, Jingjing; Dong, Lijun; Zhang, Yi; Shi, Yi; Rong, Ruiming

doi:10.1038/s41419-022-05305-7

Cited by 30 publications

(10 citation statements)

References 39 publications

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“…However, exosomes can positively or negatively exert modulatory effects, depending on their origin and cargo. Indeed, emerging evidence has suggested the therapeutic effects of MSC-derived exosomes [31][32][33]. Furthermore, through high-throughput sequencing of small RNAs in exosomes, we screened for the increased expression of miR-216a-5p, with a gene enrichment analysis revealing the involvement of the target gene of TLR4 in the in ammatory pathways, implying the hepatoprotective effect of miR-216a-5p.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation

Liu¹,

Huang²,

Wang³

et al. 2023

Preprint

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Macrophages and neutrophil play a key role in the initiation and recovery of liver ischemia reperfusion injury (IRI) through transitions in the phenotype and induces inflammation, However, the mechanisms governing these damages have yet to be fully elucidated. Exosomes have emerged as an important mediator of cellular crosstalk in various physiological and pathological processes. This study explored the role of exosomal miRNA in macrophage polarization and liver IRI. Through high-throughput sequencing of small RNAs in exosomes, we identified the negative regulator miR-216a-5p in liver IRI. Mechanistically, miR-216a-5p skewed M2 macrophage polarization and inhibited neutrophil infiltration by targeting TLR4. In conclusion, we demonstrated that exosome-derived miR-216a-5p favors an anti-inflammatory environment by promoting the M2 polarization of macrophages and inhibiting the neutrophil inflammatory response by targeting the TLR4/NF-κB and PI3K/AKT signaling pathways, revealing the endogenous protective mechanism in liver IRI.

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Section: Discussionmentioning

confidence: 99%

Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation

Liu¹,

Huang²,

Wang³

et al. 2023

Preprint

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“…Epigenetic therapies represent promising alternatives to slow down renal fibrosis progression as they can target pathways present in fibrotic niches, which refer to the microenvironments where scarring occurs [112]. Several ncRNAs, such as miR-29b [114], miR-122a [115], miR-21a-5p [116], lncRNA CRNDE as well as miR-29a-3p [117], and miR-26a-5p [118], have been shown to attenuate renal fibrosis. Therefore, they have the potential to be targeted through therapeutic approaches in order to treat renal fibrosis.…”

Section: Therapeutic Inferences Of Mirnas and Lncrnas In Renal Fibrosismentioning

confidence: 99%

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Bravo-Vázquez,

Paul,

Colín-Jurado

et al. 2024

Genes

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MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.

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“…The miR-21a-5p carried by BMMSC EVs can effectively suppress the expression of phosphofructokinase muscle isoform, which is the rate-limiting enzyme in glycolysis, thereby reducing glycolytic activity in TECs. Consequently, this mechanism contributes to the amelioration of renal fibrosis in UUO mice ( Xu et al, 2022 ).…”

Section: Therapeutic Role Of Evs In Chronic Kidney Diseasementioning

confidence: 99%

Extracellular vesicles in chronic kidney disease: diagnostic and therapeutic roles

Zheng,

Wang,

et al. 2024

Front. Pharmacol.

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Chronic kidney disease (CKD) is a progressive disorder characterized by structural and functional changes in the kidneys, providing a global health challenge with significant impacts on mortality rates. Extracellular vesicles (EVs), are vital in the physiological and pathological processes associated with CKD. They have been shown to modulate key pathways involved in renal injury, including inflammation, fibrosis, apoptosis, and oxidative stress. Currently, the application research of EVs in the diagnosis and treatment of CKD is highly prevalent. However, there is currently a lack of standardized guidelines for their application, and various methodologies have advantages and limitations. Consequently, we present an comprehensive summary elucidating the multifaceted involvement of EVs in both physiological and pathological aspects in CKD. Furthermore, we explore their potential as biomarkers and diverse therapeutic roles in CKD. This review provides an overview of the current state of research on application of EVs in the diagnosis and therapeutic management of CKD.

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Bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates renal fibrosis by attenuating glycolysis by targeting PFKM

Cited by 30 publications

References 39 publications

Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation

Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Extracellular vesicles in chronic kidney disease: diagnostic and therapeutic roles

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