miR-21-5p: A viable therapeutic strategy for regulating intraocular pressure

Tan, Chen; Song, Maomao; Stamer, W. Daniel; Qiao, Yunsheng; Chen, Xueli; Sun, Xinghuai; Lei, Yuan; Chen, Junyi

doi:10.1016/j.exer.2020.108197

Cited by 16 publications

(28 citation statements)

References 45 publications

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“…As an extensively studied miRNA, miR-21 can mediate inflammation [ 70 ], oxidative stress [ 71 ], cell apoptosis [ 72 ], proliferation [ 73 ], and regulate multiple signal pathways, including the protein kinase B (AKT) signaling pathway [ 74 , 75 ], extracellular regulated protein kinases (ERK) signaling pathway [ 76 , 77 ], and nuclear factor kappa-B (NF- κ B) [ 78 ]. Plenty of studies have proven that miR-21 participates in the occurrence and development of tumors [ 79 , 80 ], cardiovascular [ 81 ] and lung diseases [ 82 , 83 ], glaucoma intraocular pressure [ 84 ], age-related skin wound healing [ 85 ], sepsis, and acute kidney injury [ 86 ]. Moreover, it is expected to be a potential marker for the diagnosis of diseases, such as colon cancer [ 87 ], liver cancer or hepatitis severity [ 88 ], colorectal cancer [ 89 ], and lung adenocarcinoma [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Liu

Yang

Mou

et al. 2022

Oxidative Medicine and Cellular Longevity

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Purpose. Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome-mediated miRNA-21 (miR-21) transmission. Furthermore, the effects of Schwann cells- (SC-) derived exosomes on the overexpression of miR-21 for the treatment of PNI were investigated. Methods. A sciatic nerve injury model of rat was constructed, and the expression of miR-21 in serum exosomes and damaged local nerves was detected using RT-qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR-21-5p-sponge used for the knockdown of miR-21 were used to clarify the effects of exosomal miR-21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR-21 were detected using RT-qPCR analysis. Subsequently, the transmission of exosomal miR-21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR-21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC-derived exosomes overexpressing miR-21. Results. We found that EA inhibited the release of serum exosomal miR-21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR-21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR-21 was downregulated in local injury tissue via the miR-21-5p-sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR-21 enhanced the effects of the exosomes. In addition, exosomal miR-21 secreted by SC could promote neurite outgrowth in vitro. Conclusion. Our results demonstrated the mechanism of EA on PNI from the perspective of exosome-mediated miR-21 transport and provided a theoretical basis for the use of exosomal miR-21 as a novel strategy for the treatment of PNI.

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Section: Discussionmentioning

confidence: 99%

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Liu

Yang

Mou

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In the eye, many miRNAs have been found to be abundantly expressed and play important roles in ocular physiology and pathology. These include miR-200 [ 64 ] miR-184 [ 65 ] miR-29 family [ 66 ] and miR-21 [ 67 ]. Expression profiling of miRNAs in the anterior segment of healthy donors including cornea, TM, and ciliary body samples reported 378 miRs collectively expressed [ 68 ].…”

Section: Micrornas That Regulate Tgf-β Signallingmentioning

confidence: 99%

The Role of miR-29 Family in TGF-β Driven Fibrosis in Glaucomatous Optic Neuropathy

Smyth

Callaghan

Willoughby

et al. 2022

IJMS

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Primary open angle glaucoma (POAG), a chronic optic neuropathy, remains the leading cause of irreversible blindness worldwide. It is driven in part by the pro-fibrotic cytokine transforming growth factor beta (TGF-β) and leads to extracellular matrix remodelling at the lamina cribrosa of the optic nerve head. Despite an array of medical and surgical treatments targeting the only known modifiable risk factor, raised intraocular pressure, many patients still progress and develop significant visual field loss and eventual blindness. The search for alternative treatment strategies targeting the underlying fibrotic transformation in the optic nerve head and trabecular meshwork in glaucoma is ongoing. MicroRNAs are small non-coding RNAs known to regulate post-transcriptional gene expression. Extensive research has been undertaken to uncover the complex role of miRNAs in gene expression and miRNA dysregulation in fibrotic disease. MiR-29 is a family of miRNAs which are strongly anti-fibrotic in their effects on the TGF-β signalling pathway and the regulation of extracellular matrix production and deposition. In this review, we discuss the anti-fibrotic effects of miR-29 and the role of miR-29 in ocular pathology and in the development of glaucomatous optic neuropathy. A better understanding of the role of miR-29 in POAG may aid in developing diagnostic and therapeutic strategies in glaucoma.

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“…Various miRNAs are abundantly expressed in the human eye and have a clear functional disposition to be used as biomarkers to assist in the early diagnosis of POAG [82][83][84]. Several miRNAs were mentioned as POAG treatment points of interest [85].…”

Section: Functional Roles Of Specific Mirnas Found In the Aqueous Hummentioning

confidence: 99%

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

Tabak

Schreiber‐Avissar

Beit‐Yannai

2021

IJMS

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Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

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miR-21-5p: A viable therapeutic strategy for regulating intraocular pressure

Cited by 16 publications

References 45 publications

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

The Role of miR-29 Family in TGF-β Driven Fibrosis in Glaucomatous Optic Neuropathy

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

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