Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway

Li, Tangying; Quan, Huibiao; Zhang, Huachuan; Lin, Leweihua; Ou, Qianying; Chen, Kaining

doi:10.1080/21655979.2020.1823729

Cited by 14 publications

(4 citation statements)

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“…Therefore, we designed a study on the direct effect of empagliflozin on pancreatic β cells in vitro . Pancreatic β cells attacked by high glucose are a common diabetic cell model since insulin deficiency caused by pancreatic β cells dysfunction is an important pathogenic factor of diabetes mellitus [ 27 , 43 , 44 ]. Consistent with previous studies [ 45–47 ], using the CCK-8 assay, we found that the higher the concentration of glucose, the lower the activity of pancreatic β cells.…”

Section: Discussionmentioning

confidence: 99%

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Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

et al. 2021

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Diabetes mellitus is an important public health problem worldwide. Insulin deficiency caused by pancreatic β cell dysfunction is an important pathogenic factor of diabetes mellitus. This study evaluated whether empagliflozin (EMPA) protects the pancreas from diabetes mellitus-induced injury by downregulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/Gasdermin D (GSDMD) pyroptosis-related inflammasome pathway in vitro and in vivo. In vivo , animals were separated into blank control (control, C57/bl6j wild-type mice), diabetes model (db/db mice, BKS-Lepr em2Cd479 /Gpt mice), and db/db mice+EMPA (db/db+EMPA) groups. In vitro , pancreatic β cells were separated into low glucose (control), high glucose (HG), and HG+EMPA groups. The db/db+EMPA group were administered empagliflozin at 10 mg/(kg·day) by gavage for six months. Histological changes in the pancreatic tissues were observed by hematoxylin-eosin staining, and levels of the pyroptosis-related inflammatory factors NLPR3, caspase-1, and GSDMD were measured by immunohistochemistry and immunofluorescence staining methods. The Cell Counting Kit-8 assay was used to detect the effect of different concentrations of glucose and empagliflozin on the proliferation of mouse insulinoma islet β (β TC-6) cells. NLRP3/caspase-1/GSDMD expression was assessed by western blotting and immunofluorescent labeling in the β TC-6 cells. The results showed that empagliflozin reduced the pathological changes and inflammatory cell infiltration in the pancreatic tissues of db/db mice. Furthermore, empagliflozin not only reduced the expression levels of NLRP3/caspase-1/GSDMD in vitro , but also reduced their expression levels in vivo . In summary, our data suggested that empagliflozin protects the pancreatic tissues from diabetes mellitus-induced injury by downregulating the NLRP3/caspase-1/GSDMD pyroptosis-related inflammasome pathway.

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Section: Discussionmentioning

confidence: 99%

“…High glucose group: complete culture medium with 6 g/L glucose; C. High glucose+EMPA group: cells were pretreated with 6 g/L high glucose complete medium for 2 h, and then an appropriate amount of empagliflozin was added at a concentration of 200 nmol/L in the complete medium. All the groups were processed for 24 h [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

et al. 2021

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“…The signal pathways regulating the actions of CCL20 in breast cancer are diverse and complex, where the activation of a pathway signals several other downstream pathways. Besides the well-known functions of nuclear factor-kB (NF-kB) in regulating immune response and inflammation [ 105 , 106 ], increasing evidence supports their involvement in several oncogenic processes [ 105 , 107 ]. They are known to regulate the expression of proinflammatory genes, including those encoding chemokines and cytokines [ 106 ].…”

Section: Signal Pathways Regulating Ccl20 In Breast Cancermentioning

confidence: 99%

Multifaceted roles of CCL20 (C-C motif chemokine ligand 20): mechanisms and communication networks in breast cancer progression

et al. 2021

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Emerging studies have demonstrated notable roles of CCL20 in breast cancer progression. Based on these findings, CCL20 has become a potential therapeutic target for cancer immunotherapy. Accordingly, studies utilizing monoclonal antibodies to target CCL20 are currently being experimented. However, the existence of cytokine network in the tumor microenvironment collectively regulates tumor progression. Hence, a deeper understanding of the role of CCL20 and the underlying signaling pathways regulating the functions of CCL20 may provide a novel strategy for therapeutic interventions. This review provides the current knowledge on how CCL20 interacts with breast cancer cells to influence tumor progression via immunosuppression, angiogenesis, epithelial to mesenchymal transition, migration/invasion and chemoresistance. As a possible candidate biomarker, we also reviewed signal pathways and other factors in the tumor microenvironment regulating the tumor-promoting functions of CCL20.These new insights may be useful to design new potent and selective CCL20 inhibitors against breast cancer in the future.

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“…Inhibition of CyPA can promote insulin secretion, reduce the pancreatic β cell apoptosis caused by high glucose, and alleviate inflammation and oxidative stress. [10] CyPA is involved in inflammatory reactions, which is closely related to diabetes and atherosclerosis. [11] CyPA is also a newly identified RNA binding protein.…”

Section: Introductionmentioning

confidence: 99%

The effect of overexpression of CyPA on gene expression in human umbilical vein endothelial cells

Yang,

Zhou,

et al. 2024

Medicine

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The aim of this study is to screen the differentially expressed genes and genes with alternative splicing in PPIA overexpressing cells by transcriptome sequencing. Transcriptome sequencing was performed to identify differentially expressed genes and genes with altered alternative splicing in PPIA overexpressing cells and results were validated by real-time quantitative polymerase chain reaction. The biological function and pathways of those genes were further explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 157 significantly upregulated genes and 171 significantly downregulated genes were identified in PPIA overexpressing cells, and the splicing pattern of LHPP, APH1A, BRD1, and ORAI3 was found to be altered. GO analyses showed that the most enriched GO terms of the 157 upregulated genes included extracellular region, protein binding, and metal ion, and the most enriched GO terms of the 171 downregulated genes included binding neuron projection, protein binding, and endoplasmic reticulum unfolded protein response. Kyoto Encyclopedia of Genes and Genomes analyses showed that the 157 upregulated genes were mainly enriched in gastric acid secretion, Mitogen-activated protein kinase signaling pathway, etc, and the 171 downregulated genes were mainly enriched in transcriptional misregulation in cancer, Tumor necrosis factor signaling pathway, etc. The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes and induces alternative splicing in multiple genes. PPIA alters the expression or the alternative splicing pattern of downstream genes, leading to pathogenesis of vascular endothelial injury by high glucose mediated through CyPA.

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Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway

Abstract: (2020) Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway,

Cited by 14 publications

References 50 publications

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

Empagliflozin protects diabetic pancreatic tissue from damage by inhibiting the activation of the NLRP3/caspase-1/GSDMD pathway in pancreatic β cells: in vitro and in vivo studies

Multifaceted roles of CCL20 (C-C motif chemokine ligand 20): mechanisms and communication networks in breast cancer progression

The effect of overexpression of CyPA on gene expression in human umbilical vein endothelial cells

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