Melatonin inhibits Müller cell activation and pro‐inflammatory cytokine production via upregulating the MEG3/miR‐204/Sirt1 axis in experimental diabetic retinopathy

Tu, Yuanyuan; Zhu, Manhui; Wang, Zhenzhen; Wang, Kun; Chen, Lili; Liu, Wangrui; Shi, Qin; Zhao, Qingliang; Sun, Yake; Wang, Xiaoyu; Song, E; Liu, Xiaojuan

doi:10.1002/jcp.29716

Cited by 53 publications

(31 citation statements)

References 43 publications

(69 reference statements)

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“…In normal conditions, only retinal astrocytes express glial fibrillary acidic protein (GFAP); however, in DR, there is upregulation of this intermediate filament protein in Müller cells, which can be used as a marker of reactive gliosis in the retina [95]. Moreover, activated Müller cells secrete various inflammatory cytokines resulting from the overexpression of innate immunerelated pathways [96,97]. Müller cell studies using diabetic animal models have proposed a potential important role of these cells in retinal water imbalance and vascular abnormalities [58,98].…”

Section: Reactive Gliosis In Drmentioning

confidence: 99%

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

Shen¹,

Lo²,

Mi³

et al. 2021

Eye and Vis

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Diabetic retinopathy (DR), one of the common complications of diabetes, is the leading cause of visual loss in working-age individuals in many industrialized countries. It has been traditionally regarded as a purely microvascular disease in the retina. However, an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina. Deterioration of neural retina could precede microvascular abnormalities in the DR, leading to microvascular changes. Furthermore, disruption of interactions among neurons, vascular cells, glia and local immune cells, which collectively form the neurovascular unit, is considered to be associated with the progression of DR early on in the disease. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration, neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR. Here, we present current perspectives on the pathophysiology of DR as a neurovascular disease, especially at the early stage. Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.

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Section: Reactive Gliosis In Drmentioning

confidence: 99%

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

Shen¹,

Lo²,

Mi³

et al. 2021

Eye and Vis

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“…These findings suggest that the miR-23b-3p/SIRT1/NF-κB feedback loop may exert a crucial role in the establishment and maintenance of metabolic memory in DR ( 87 ). In addition, inhibition of miR-211, miR-29b-3p, miR-221, miR-34a, miR-217, miR-195, miR-377, miR-543, and miR-204 was also reported to upregulate the expression of SIRT1 and improve DR by alleviating apoptosis, inflammation, oxidative stress, angiogenesis, and ER stress ( 88 – 97 ).…”

Section: The Role Of Sirt1 In Microvascular Complicationsmentioning

confidence: 99%

“…Another SIRT1 agonist, N-acetyl-5-methoxytryptamine, commonly known as melatonin, has been revealed to exert its protective properties in DCM through the prevention of Drp1-mediated mitochondrial fission by SIRT1/PGC1-α pathway ( 37 ). Another study showed that melatonin could also inhibit pro-inflammatory cytokine production in the progression of DR ( 97 ). Recently, Xue et al.…”

Section: Sirt1 As a Potential Drug Target For The Treatment Of Diabetmentioning

confidence: 99%

Epigenetic Regulation Associated With Sirtuin 1 in Complications of Diabetes Mellitus

Wang

et al. 2021

Front. Endocrinol.

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Diabetes mellitus (DM) has been one of the largest health concerns of the 21st century due to the serious complications associated with the disease. Therefore, it is essential to investigate the pathogenesis of DM and develop novel strategies to reduce the burden of diabetic complications. Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, has been reported to not only deacetylate histones to modulate chromatin function but also deacetylate numerous transcription factors to regulate the expression of target genes, both positively and negatively. SIRT1 also plays a crucial role in regulating histone and DNA methylation through the recruitment of other nuclear enzymes to the chromatin. Furthermore, SIRT1 has been verified as a direct target of many microRNAs (miRNAs). Recently, numerous studies have explored the key roles of SIRT1 and other related epigenetic mechanisms in diabetic complications. Thus, this review aims to present a summary of the rapidly growing field of epigenetic regulatory mechanisms, as well as the epigenetic influence of SIRT1 on the development and progression of diabetic complications, including cardiomyopathy, nephropathy, and retinopathy.

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“…qRT-PCR was conducted with the powerUP SYBR Green Master Mix (Thermo Fisher Scienti c, USA). qRT-PCR was also performed [10]. The primers used in this study is showed in the Supplemental table 1.…”

Section: Quantitative Real-time Pcr (Qrt-pcr)mentioning

confidence: 99%

“…The western blot analysis was conducted [10]. In brief, the cultured Müller cells and the mice retina were collected and lysed with protein lysate.…”

Section: Western Blotmentioning

confidence: 99%

Knockdown of KCNQ1OT1 Alleviates the Activation of NLRP3 Inflammasome Through miR-17-5p/TXNIP Axis in Retinal Müller Cells

Liu¹,

Cao²,

Dong³

et al. 2021

Preprint

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Diabetic retinopathy (DR) is one of the most severe and common complications caused by diabetic mellites. Inhibiting NLRP3 inflammasome activation displays a crucial therapeutic value in DR. Studies have shown that KCNQ1OT1 plays a critical role in regulating NLRP3 inflammasome activation and participates in the pathogenesis of diabetic complications. The present study aims to explore the role, and the potential mechanism of KCNQ1OT1 in regulating the activation of NLRP3 inflammasome in DR. The expression of KCNQ1OT1 and the activation of NLRP3 inflammasome were increased in experimental DR models. KCNQ1OT1 knockdown alleviated NLRP3 inflammasome-associated molecules expression. In addition, KCNQ1OT1 was found to be localized mainly in the cytoplasm of Müller cells and facilitated TXNIP expression by acting as a miR-17-5p sponge. KCNQ1OT1 promoted the activation of NLRP3 inflammasome through miR-17-5p/TXNIP axis. Moreover, the clinical samples of patients with DR showed that the expression of KCNQ1OT1 and the activation of NLRP3 inflammasome were all increased, further supporting the hypothesis that the KCNQ1OT1 dysregulation may be the molecular mechanism of the pathogenesis of DR. Therefore, KCNQ1OT1 may serve as a new therapeutic target for DR.

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Melatonin inhibits Müller cell activation and pro‐inflammatory cytokine production via upregulating the MEG3/miR‐204/Sirt1 axis in experimental diabetic retinopathy

Cited by 53 publications

References 43 publications

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

Epigenetic Regulation Associated With Sirtuin 1 in Complications of Diabetes Mellitus

Knockdown of KCNQ1OT1 Alleviates the Activation of NLRP3 Inflammasome Through miR-17-5p/TXNIP Axis in Retinal Müller Cells

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