Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration

Gnanaguru, Gopalan; Wagschal, Alexandre; Oh, Justin D.; Saez‐Torres, Kahira L.; Li, Tong; Temel, Ryan E.; Kleinman, Mark E.; Näär, Anders M.; D’Amore, Patricia A.

doi:10.1016/j.ymthe.2021.03.014

Cited by 13 publications

(5 citation statements)

References 68 publications

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“…Although multiple animal experiments have confirmed that miR-33 is an important small RNA in regulating lipid metabolism, few studies have been conducted on its expression levels in circulating blood in individuals with hyperlipidemia (20,58,(63)(64)(65)(66)(67). A total of two studies have confirmed upregulation of miR-33 expression in circulating blood using different methods in participants with hyperlipidemia compared with participants without hyperlipidemia (68,69).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid β-oxidation via the microRNA-33/SIRT6 signaling pathway

Liu,

Pan,

Hao

et al. 2024

Exp Ther Med

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Hyperlipidemia is a strong risk factor for numerous diseases. Resveratrol (Res) is a non-flavonoid polyphenol organic compound with multiple biological functions. However, the specific molecular mechanism and its role in hepatic lipid metabolism remain unclear. Therefore, the aim of the present study was to elucidate the mechanism underlying how Res improves hepatic lipid metabolism by decreasing microRNA-33 (miR-33) levels. First, blood miR-33 expression in participants with hyperlipidemia was detected by reverse transcription-quantitative PCR, and the results revealed significant upregulation of miR-33 expression in hyperlipidemia. Additionally, after transfection of HepG2 cells with miR-33 mimics or inhibitor, western blot analysis indicated downregulation and upregulation, respectively, of the mRNA and protein expression levels of sirtuin 6 (SIRT6). Luciferase reporter analysis provided further evidence for binding of miR-33 with the SIRT6 3'-untranslated region. Furthermore, the levels of peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ-coactivator 1α and carnitine palmitoyl transferase 1 were increased, while the concentration levels of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory element-binding protein 1 were decreased when SIRT6 was overexpressed. Notably, Res improved the basic metabolic parameters of mice fed a high-fat diet by regulating the miR-33/SIRT6 signaling pathway. Thus, it was demonstrated that the dysregulation of miR-33 could lead to lipid metabolism disorders, while Res improved lipid metabolism by regulating the expression of miR-33 and its target gene, SIRT6. Thus, Res can be used to prevent or treat hyperlipidemia and associated diseases clinically by suppressing hepatic fatty acid synthesis and increasing fatty acid β-oxidation.

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Section: Discussionmentioning

confidence: 99%

Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid β-oxidation via the microRNA-33/SIRT6 signaling pathway

Liu,

Pan,

Hao

et al. 2024

Exp Ther Med

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“…Our analyses showed that oni-miR-33/mir-33 shares a high sequence similarity with those in other organisms, suggesting that miR-33 is highly conserved and may be a key regulator. In fact, miR-33 has been reported to be involved in age-related macular degeneration [ 42 ], inflammatory responses [ 43 ], and cell proliferation in mice [ 44 ]. The differential expression of miR-33 in tilapia ovarian tissue under heat stress provides new clues about its role in regulating follicular atresia.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-33 Exacerbates Heat-Stress-Induced Apoptosis in Granulosa Cell and Follicular Atresia of Nile Tilapia (Oreochromis niloticus) by Targeting TGFβ1I1

Qiang

Tao

et al. 2022

Genes

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High temperature affects egg quality and increases follicular atresia in teleosts. The present study aimed to explore the regulated mechanism of ovary syndrome of Nile tilapia (Oreochromis niloticus) exposed to heat stress. To this end, we conducted histological and biochemical analyses and integrated miRNA-target gene analyses. The histochemical analyses confirmed that heat stress promoted the apoptosis of granulosa cell and therefore resulted in increased follicular atresia in the ovary. Heat stress led to the differential expression of multiple miRNAs (miR-27e, -27b-3p, -33, -34a -133a-5p, and -301b-5p). In a luciferase activity assay, miR-33 bound to the 3′-untranslated region (UTR) of the TGFβ1I1 (transforming growth factor-β1-induced transcript 1) gene and inhibited its expression. A TGFβ1I1 gene signal was detected in the granulosa cells of Nile tilapia by immunohistochemical analysis. Up-regulation of the miR-33 of tilapia at 6 d and 12 d exposed to heat (34.5 °C ± 0.5 °C) had significant down-regulation of the TGFβ1I1 expression of the gene and protein in tilapia ovaries. An miRNA-target gene integrated analysis revealed that miR-33 and TGFβ1I1 function in an apoptosis-related signal pathway. The signal transduction of the vascular endothelial growth factor (VEGF) family members VEGFA and its receptor (KDR) in the heat-stressed group decreased significantly compared with the control group. Transcript-levels of the Bax and Caspase-3 as apoptotic promotors were activated and Bcl-2 and Caspase-8 as apoptotic inhibitors were suppressed in the heat-stressed tilapia. These results suggest that heat stress increases the expression of miR-33, which targets TGFβ1I1 and inhibits its expression, resulting in decreased levels of follicle-stimulating hormone and 17β-estradiol and increased apoptosis by suppressing VEGF signaling, eventually inducing follicular atresia. In conclusion, our results show that the miR-33/TGFβ1I1 axis of Nile tilapia is involved in the follicular development of broodstock, and can suppress VEGF signaling to accelerate follicular atresia. Our findings demonstrate the suppressive role of miR-33 during oocyte development in Nile tilapia.

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“…While our current grasp of cholesterol metabolism in the eye is not exhaustive, we believe eye diseases are closely linked to abnormal cholesterol metabolism. Simultaneously, we have identified numerous potential therapeutic targets and summarized them in this review (Table 4), [243][244][245] with the aim of fostering a more comprehensive understanding of disease prevention and treatment in the future.…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Cholesterol metabolism: physiological regulation and diseases

Guo,

Chen,

Zhang

et al. 2024

MedComm

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Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset of cardiovascular disease (CVD) but is also the fundamental cause of other ailments. The regulation of cholesterol metabolism in the human is an extremely complex process. Due to the dynamic balance between cholesterol synthesis, intake, efflux and storage, cholesterol metabolism generally remains secure. Disruption of any of these links is likely to have adverse effects on the body. At present, increasing evidence suggests that abnormal cholesterol metabolism is closely related to various systemic diseases. However, the exact mechanism by which cholesterol metabolism contributes to disease pathogenesis remains unclear, and there are still unknown factors. In this review, we outline the metabolic process of cholesterol in the human body, especially reverse cholesterol transport (RCT). Then, we discuss separately the impact of abnormal cholesterol metabolism on common diseases and potential therapeutic targets for each disease, including CVD, tumors, neurological diseases, and immune system diseases. At the end of this review, we focus on the effect of cholesterol metabolism on eye diseases. In short, we hope to provide more new ideas for the pathogenesis and treatment of diseases from the perspective of cholesterol.

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Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration

Cited by 13 publications

References 68 publications

Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid β-oxidation via the microRNA-33/SIRT6 signaling pathway

Resveratrol suppresses hepatic fatty acid synthesis and increases fatty acid β-oxidation via the microRNA-33/SIRT6 signaling pathway

Upregulation of miR-33 Exacerbates Heat-Stress-Induced Apoptosis in Granulosa Cell and Follicular Atresia of Nile Tilapia (Oreochromis niloticus) by Targeting TGFβ1I1

Cholesterol metabolism: physiological regulation and diseases

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