The significance of Akt/NF-κb signaling pathway in the posterior cataract animal model

Shao, Danbing; Zhu, Xinqun; Huo, Longwei; Sun, Wenqiang; Pan, Peng; Chen, W.; Wang, H.; Liu, B.

doi:10.4149/bll_2017_082

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Phosphorylation of Akt is promoted by PDK-1 and PDK-2; it affects cell growth, cell cycle entry, and cell survival 29 . Then it regulates signaling pathways and induces the expression of NF-kB family; it has been reported that Akt serine/threonine kinase is involved in the induction of NF-kB 30,31 . Previous studies have shown that NF-kB can regulate the production of inflammatory mediators, which is positively correlated with the development of OA 22,23 .…”

Section: Discussionmentioning

confidence: 99%

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

Chen

2020

Cell Transplant

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In osteoarthritis (OA), the synthesis and decomposition of the extracellular matrix (ECM) are imbalanced. High expression levels of Wnt1-inducible signaling pathway protein 1 (WISP1) promote the synthesis of matrix metalloproteinases and induce the degradation of cartilage, which aggravates the OA. The aim of this study was to explore the role of miR-128-3p in the development of OA. In the present study, the expression of WISP1 and miR-128-3p in osteoarthritic tissues and chondrocytes was detected using quantitative reverse transcription PCR (RT-qPCR) and Western blotting. Then we predicted that WISP1 might be a potential target gene of miR-128-3p by TargetScan and verified using luciferase reporter gene assay. The effect of miR-128-3p or WISP1 on chondrocytes was evaluated by cell proliferation assay, apoptosis, and caspase-3 activity assay. To further reveal the molecular mechanisms of miR-128-3p in osteoarthritic development, the degradation of chondrocyte matrix and production of proinflammatory cytokines in osteoarthritic chondrocyte model were detected by ELISA. To mimic the osteoarthritic microenvironment in vitro studies, chondrocytes were stimulated with interleukin (IL)-1β, and then we found that the expression of miR-128-3p was downregulated. Overexpression of WISP1 inhibited the proliferation of chondrocytes, which induced apoptosis, degradation of chondrocyte matrix, production of proinflammatory cytokines, and activated the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Then, we identified that miR-128-3p was a negative regulator of WISP1 by directly targeting its 3′-untranslated region (UTR). Moreover, the PI3K allosteric activator 740 Y-P abolished the inhibition of miR-128-3p in apoptosis, degradation of chondrocyte matrix, and inflammation. Our results showed that miR-128-3p targets WISP1 to regulate chondrocyte proliferation, apoptosis, degradation of chondrocyte matrix, and production of proinflammatory cytokines via the PI3K/Akt/NF-κB pathway, which plays a suppressed role in OA.

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Section: Discussionmentioning

confidence: 99%

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

Chen

2020

Cell Transplant

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“…Among which, NF‐κB has been proposed as a therapeutic target for the treatment of cataracts (Chung et al, ). And NF‐κB signaling is closely related to the occurrence and development of posterior capsular opacification (Shao et al, ). Thus, herein, we investigated the regulatory effect of Tanshinone IIA on NF‐κB signaling.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA protects lens epithelial cells from H₂O₂‐induced injury by upregulation of lncRNA ANRIL

Wang²,

Zhang

et al. 2019

Journal Cellular Physiology

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Tanshinone IIA is a lipophilic diterpene extracted from the Salvia miltiorrhiza bunge, possessing antiapoptotic and antioxidant activities. The purpose of this study was to explore the effects of Tanshinone IIA on age‐related nuclear cataract. Human lens epithelial cell line SRA01/04 was subjected to H 2O 2 to mimic a cell model of cataract. Cell Counting Kit‐8 assay, flow cytometer, and reactive oxygen species (ROS) detection were performed to evaluate the effect of Tanshinone IIA pretreatment on SRA01/04 cells injured by H 2O 2. Besides, the real‐time quantitative polymerase chain reaction was used to assess the expression of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL). Western blot analysis was performed to detect the expression of core proteins involved in cell survival and nuclear factor‐κB (NF‐κB) pathway. H 2O 2 significantly decreased SRA01/04 cells viability, whereas increased apoptosis and ROS generation. This phenomenon was coupled with the upregulated p53, p21, Bax, cleaved caspase‐3, and the downregulated cyclinD1, CDK4, and Bcl‐2. Tanshinone IIA pretreatment protected SRA01/04 cells against H 2O 2‐induced injury. In the meantime, the expression of lncRNA ANRIL was upregulated by Tanshinone IIA. And, the protective effects of Tanshinone IIA on H 2O 2‐stimulated SRA01/04 cells were abolished when lncRNA ANRIL was silenced. Moreover, the elevated expression of lncRNA ANRIL induced by Tanshinone IIA was abolished by BAY 11‐7082 (an inhibitor of NF‐κB). To conclude, Tanshinone IIA protects SRA01/04 cells from apoptosis triggered by H 2O 2. Tanshinone IIA confers its protective effects possibly via modulation of NF‐κB signaling and thereby elevating the expression of lncRNA ANRIL.

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Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling

et al. 2019

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Backgrounds/Aims: To explore whether NLRP3 is involved in the development of cataract and to study the effect of NLRP3 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells. Methods: Oxidative stress-induced apoptosis model was constructed by treating HLEB3 cells with 50 µM H2O2 at different times (6 h, 12 h) and was confirmed by flow cytometry and Western blot. HLEB3 were divided into NC, NC+H2O2, shNLRP3, and shNLRP3+H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, DCFH-DA to measure reactive oxygen species production, and Annexin V-FITC/PI staining to determine cell apoptosis. Results: NLRP3 expression significantly increased in H2O2-induced HLEB3 cells. shRNA interference of NLRP3 inflammasome protects HLEB3 cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase-3 and Bax and increasing Bcl-2 expression. shNLRP3 was able to effectively suppress H2O2-induced apoptosis via inhibition of NF-κB signaling. Conclusion: NLRP3 might be involved in the apoptosis of lens epithelial cells. The inhibition of NLRP3 obviously attenuated H2O2-induced oxidative stress injury of human lens epithelial cells via NF-κB signaling.

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The significance of Akt/NF-κb signaling pathway in the posterior cataract animal model

Cited by 3 publications

References 13 publications

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

Tanshinone IIA protects lens epithelial cells from H₂O₂‐induced injury by upregulation of lncRNA ANRIL

Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling

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The significance of Akt/NF-κb signaling pathway in the posterior cataract animal model

Cited by 3 publications

References 13 publications

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

MiR-128-3p Post-Transcriptionally Inhibits WISP1 to Suppress Apoptosis and Inflammation in Human Articular Chondrocytes via the PI3K/AKT/NF-κB Signaling Pathway

Tanshinone IIA protects lens epithelial cells from H2O2‐induced injury by upregulation of lncRNA ANRIL

Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling

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Tanshinone IIA protects lens epithelial cells from H₂O₂‐induced injury by upregulation of lncRNA ANRIL