Proanthocyanidins attenuate the high glucose‐induced damage of retinal pigment epithelial cells by attenuating oxidative stress and inhibiting activation of the NLRP3 inflammasome

Li, Hongsong; Li, Rong; Wang, Lijun; Liao, Ding-Ying; Zhang, Wenyi; Wang, Jianming

doi:10.1002/jbt.22845

Cited by 16 publications

(7 citation statements)

References 32 publications

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“…As mentioned earlier, the key points in the pathogenesis of this complication are oxidative stress and inflammation [ 22 ]. There are research reports that Procyanidin may protect RPE cells from high glucose-induced injury through the p53/mTOR autophagy pathway [ 23 ], Proanthocyanidins (PACs) can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR [ 24 ]. CAR has been previously mentioned to ameliorate oxidative stress, inflammatory response, as well as cellular damage.…”

Section: Discussionmentioning

confidence: 99%

Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose

Wang

2021

Bioengineered

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Diabetic retinopathy (DR) is the most prominent manifestation of diabetic microangiopathy and is a serious complication of diabetes. Despite extensive researches focusing on DR, treatment options for DR are still limited. Carvedilol (CAR) has vasodilatory, antioxidant stress and anti-inflammatory effects and poses a vital role in addressing the issue of diabetic complications. This paper attempts to explore this property of CAR and investigate into its effects on DR. First, ARPE-19 cells were treated with different concentrations of CAR and cells were induced with 30 mM high glucose (HG) to establish a DR cell model. Cell viability was assayed by cell counting kit-8 (CCK-8) with or without HG induction. Cellular inflammation and oxidative stress were evaluated by enzyme-linked immunosorbent assay (ELISA) and corresponding kits. The measurement of apoptosis levels was conducted by Terminal dUTP nick-end labeling (TUNEL) and Western blotting. The protein levels related to Nrf2/ARE signaling pathway were assessed by Western blotting. Finally, cellular inflammation, oxidative stress and apoptosis in ARPE-19 cells pretreated with Nrf2 inhibitor ML385 were tested again by the same methods. Results showed that under HG induction, CAR effectively improved ARPE-19 cell viability, inhibited cellular inflammation, oxidative stress, and apoptosis. Moreover, CAR activated Nrf2/ARE signaling pathway, which further suppressed cellular inflammation, oxidative stress, and apoptosis. Overall, CAR inhibited HG-induced oxidative stress and apoptosis in retinal pigment epithelial cells by activating Nrf2/ARE pathway.

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Section: Discussionmentioning

confidence: 99%

Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose

Wang

2021

Bioengineered

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“…ARPE-19 cells, an adult RPE cell line (obtained from ATCC), were cultured in a medium (as instructed by ATCC guidelines, containing Dulbecco's modified Eagle medium/F12 (Gibco, USA), 10% fetal bovine serum (Invitrogen, USA)) and stored at 37°C in a humidified 5% CO 2 incubator. DNA from ARPE-19 cells was extracted and submitted for cell line authentication using a short tandem repeat analysis by Biowing Applied Biotechnology (SBWAB) Co. Ltd. (Shanghai, China) [ 15 ]. ARPE-19 cells were divided into four groups according to different treatment methods as follows: control group, PFD group, TGF- β 2 group, and PFD + TGF- β 2 group.…”

Section: Methodsmentioning

confidence: 99%

Pirfenidone Attenuates the EMT Process and the Secretion of VEGF in TGF-β2-Induced ARPE-19 Cells via Inhibiting the Activation of the NF-κB/Snail Signaling Pathway

Wang

Shao

et al. 2023

Journal of Ophthalmology

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Aim. Pirfenidone (PFD), an antifibrotic drug, has various beneficial functions such as antioxidant, antifibrotic, and anti-inflammatory effects. This study aimed to explore the molecular mechanisms underlying how PFD modulates retinal pigment epithelial (RPE) cells involved in neovascularization and subretinal fibrosis. Methods. ARPE-19 cell lines were treated with transforming growth factor-beta 2 (TGF-β2) alone or in combination with PFD. RPE cell viability, as a consequence of PFD use, was determined by the CCK-8 assay. Cell migration was assessed by the wound closure assay and quantified by the Image J software. Protein expression of the following markers was measured by the western blot analysis: an epithelial cell marker and E-cadherin; mesenchymal cell markers, fibronectin, matrix metalloprotein-9 (MMP-9), and alpha-smooth muscle actin (α-SMA); a fibrotic marker and connective tissue growth factor (CTGF); an angiogenesis marker and vascular endothelial growth factor (VEGF); NF-κB/Snail. The mRNA levels of fibronectin and α-SMA were determined by quantitative real-time PCR. VEGF was quantitatively measured by the enzyme-linked immunosorbent assay. Results. The cell viability assay revealed that PFD had no significant cytotoxic effect on RPE cells at concentrations of less than 1 mg/mL. The cell scratch assay showed that TGF-β2 stimulation significantly improved the migration of RPE cells and that PFD attenuated this effect. PFD significantly inhibited the TGF-β2-induced protein expression of E-cadherin and increased the TGF-β2-induced protein expression of fibronectin, MMP-9, α-SMA, CTGF, and VEGF in ARPE-19 cells. The mRNA expression of fibronectin and α-SMA was inhibited by PFD in TGF-β2-inducedARPE-19 cells. Additionally, the increased intracellular and supernatant expression of VEGF protein was suppressed by PFD. Mechanistically, RPE cells treated with PFD + TGF-β2 exhibited a decrease in phosphorylation of the NF-κB P65 subunit and activation of Snail, compared with the RPE cells treated with TGF-β2 alone. Conclusion. PFD ameliorated TGF-β2-induced neovascularization and fibrosis by suppressing the NF-κB/Snail signaling pathway. Therefore, PFD may be a potential drug in the treatment of age-related macular degeneration.

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“…RPEs form the external BRB and regulate the structure and functioning of the retinal, RPEs act as a cellular barrier separating the neuronal retina and the fenestrated choriocapillaris, and disruption of the RPE barrier plays a pathogenic role in the development of DR ( 4 ). A high glucose environment results in pyroptosis of RPE cells through a series of events, starting with the plasma membrane passage of glucose, which then generates mitochondrial ROS, leading to NLRP3 inflammasome activation, cleavage of CASP1, and IL-1β/18 release ( 173 ). It was shown that pyroptosis-linked proteins such as Caspase-1, GSDMD, NLRP3, and IL-1β/18 were upregulated in a high glucose environment.…”

Section: Nlrp3 and Pyroptosis In Diabetic Retinopathymentioning

confidence: 99%

The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy

2023

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In the working-age population worldwide, diabetic retinopathy (DR), a prevalent complication of diabetes, is the main cause of vision impairment. Chronic low-grade inflammation plays an essential role in DR development. Recently, concerning the pathogenesis of DR, the Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome in retinal cells has been determined as a causal factor. In the diabetic eye, the NLRP3 inflammasome is activated by several pathways (such as ROS and ATP). The activation of NPRP3 leads to the secretion of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18), and leads to pyroptosis, a rapid inflammatory form of lytic programmed cell death (PCD). Cells that undergo pyroptosis swell and rapture, releasing more inflammatory factors and accelerating DR progression. This review focuses on the mechanisms that activate NLRP3 inflammasome and pyroptosis leading to DR. The present research highlighted some inhibitors of NLRP3/pyroptosis pathways and novel therapeutic measures concerning DR treatment.

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Proanthocyanidins attenuate the high glucose‐induced damage of retinal pigment epithelial cells by attenuating oxidative stress and inhibiting activation of the NLRP3 inflammasome

Cited by 16 publications

References 32 publications

Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose

Carvedilol activates nuclear factor E2-related factor 2/ antioxidant response element pathway to inhibit oxidative stress and apoptosis of retinal pigment epithelial cells induced by high glucose

Pirfenidone Attenuates the EMT Process and the Secretion of VEGF in TGF-β2-Induced ARPE-19 Cells via Inhibiting the Activation of the NF-κB/Snail Signaling Pathway

The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy

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