The Novel KLF4/BIG1 Regulates LPS-mediated Neuro-inflammation and Migration in BV2 Cells via PI3K/Akt/NF-kB Signaling Pathway

You, Zhijun; Yang, Zhenzhen; Cao, Shuang; Shou-heng, Deng; Chen, Yi

doi:10.1016/j.neuroscience.2022.01.014

Cited by 24 publications

(16 citation statements)

References 43 publications

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“…Further, it is well-reported that NFκB activation by immune activator lipopolysaccharide (LPS) is directly regulated via phosphorylation of PI3K/Akt, which is the main upstream molecule of NFκB [44]. The PI3K/Akt/NFκB signaling axis has been proposed by several other studies using BV-2 microglia [45][46][47][48]. In agreement with these studies, we did find that the reduction of Akt phosphorylation in response to HG stimulation showed the same trend as that of NFκB p65.…”

Section: Discussionsupporting

confidence: 90%

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia

Lee,

Lin,

Hsieh

et al. 2023

Biomedicines

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Patients with diabetes mellitus can experience hyperglycemia, which affects brain function and produces cognitive impairment or neurodegeneration. Neuroinflammation is an important cause of cognitive dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycemic agents that reportedly possess anti-inflammatory properties and may produce beneficial cognitive effects. We hypothesized that SGLT2 inhibitors alleviate hyperglycemia-related inflammation in brain immune cells. Cultured BV-2 microglia were exposed to high glucose (HG) in the absence or presence of SGLT2 inhibitors including canagliflozin (Cana), dapagliflozin (Dapa), empagliflozin (Empa), and ertugliflozin (Ertu). Afterward, we evaluated the cytotoxic and inflammatory responses by specific biochemical assays. Treatments with non-toxic Cana or Dapa, but not Empa or Ertu, inhibited proliferation without cell death. Only Cana rescued BV-2 microglia from HG-induced cytotoxicity, including apoptosis or autophagic degradation. None of SGLT2 inhibitors affected the HG-stimulated induction of stress proteins HO-1 and HSP70. Also, compared to the other three SGLT2 inhibitors, Cana was better at inhibiting HG-induced oxidative/inflammatory stress, as evidenced by its ability to repress proinflammatory factors (e.g., oxygen free radicals, iNOS, NLRP3, IL-1β, and TNF-α) other than COX-2. Cana’s action to alleviate HG insults was mediated not by altering SGLT2 protein expression, but by reducing HG-stimulated signaling activities of NFκB, JNK, p38, and PI3K/Akt pathways. Particularly, Cana imitated the effects of NFκB inhibitor on HG-induced iNOS and COX-2. Of the four SGLT2 inhibitors, Cana provided BV-2 microglia with the best protection against HG-induced inflammatory toxicity. Thus, Cana may help to reduce innate neuroimmune damage caused by hyperglycemia.

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Section: Discussionsupporting

confidence: 90%

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia

Lee,

Lin,

Hsieh

et al. 2023

Biomedicines

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“…PI3K/AKT pathway plays a central role in regulating inflammatory responses, while NF-κB pathway is generally acknowledged as a prototypical proinflammatory pathway. It is generally agreed that PI3K/ Akt pathway could be an upstream activator of the NF-κB signaling cascade, thus emerging as a therapeutic target for inflammatory diseases [37][38][39]. erefore, it was deduced that regulation of PI3K/AKT/NF-κB signaling pathway could be a pivotal action mechanism of XLGB for managing inflammation in OA.…”

Section: Discussionmentioning

confidence: 99%

Multitech-Based Study on Medicinal Material Basis and Action Mechanism of Herbal Formula Xian-Ling-Gu-Bao Capsule in Treatment of Osteoarthritis

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Currently, osteoarthritis (OA) is thought to be the most prevalent chronic joint disease worldwide. The epidemiology of this disorder is complex, and the treatment is challenging. Xian-Ling-Gu-Bao (XLGB) capsule, a herbal compound preparation, is widely used for the treatment of bone disorders, including OA. Although its efficacy and safety have been demonstrated in clinical trials and practice, the underlying medicinal constituents and mechanism have not been clearly elucidated. Therefore, this study aimed to explore the medicinal constituents and mechanism of XLGB for OA treatment. The phytochemical constituents in XLGB capsule were detected by liquid chromatography-mass spectrometry (LC-MS), the medicinal constituents and therapeutic mechanism for OA treatment were deduced by network analysis, and the deduced mechanism was validated by in vitro experiment. As a result, a total of 55 constituents were detected in XLGB extract, in which 16 constituents were screened out for target collection. Based on the analysis of target profile, XLGB targets showed a high degree of similarity with OA targets. Network analysis revealed that XLGB had a holistic effect of multiple active constituents on multiple targets and pathways. The core targets of XLGB were presumed to be MAPKs, PI3K, AKT, BCL2, RELA, TNF, NOS2, and so on, and the mechanism was speculated to mainly inhibit chondrocyte apoptosis and inflammatory response through JNK and PI3K/AKT/NF-κB signaling cascades. Finally, in vitro study confirmed that XLGB extract protected ATDC5 cells against lipopolysaccharide- (LPS-) induced apoptosis and inflammatory response, and these effects were supposed to be involved in the inhibition of JNK and PI3K/AKT/NF-κB pathways. Our study could provide a scientific basis for further research and clinical use of XLGB capsule.

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“…Mechanistically, this regulatory function of KLF4 has been attributed to its ability to activate Rho-related GTPase RHOF [20]. The NF-κB signaling pathway is widely acknowledged as a pivotal pro-in ammatory pathway in various diseases, including heart failure and myocardial infarction, where it assumes a critical role in the underlying pathophysiological mechanisms [21,22]. However, the precise regulatory mechanisms of this signaling pathway in myocardial ischemia-reperfusion injury are not fully understood at present.…”

Section: Introductionmentioning

confidence: 99%

The protective effect of Iron Isomaltoside on myocardial ischemia-reperfusion injury via the suppression of KLF4/NF-κB signaling

Gong,

Zhao,

Zhang

et al. 2024

Preprint

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[Objectives] This study aimed to investigate the beneficial effects of iron isomaltoside (IIM) on myocardial function and the associated mechanisms in rats with myocardial ischemia/reperfusion (I/R)-induced damage and hypoxia/reoxygenation (H/R)-induced H9C2 cells. [Design & Methods] Changes in cardiac pathology after myocardial infarction (MI) were analyzed with hematoxylin-eosin staining. Myocardial cellapoptosis in the heart tissues of rats with MI was assessed using TUNEL staining. In H/R-induced H9C2 cells, cell viability and lactate dehydrogenase (LDH) and adenosine 5’-triphosphate levels were detected. Apoptosis and MMP in H9C2 cells were detected with flow cytometry. [Results] Our results demonstrated that IIM treatment reduced myocardial injury induced by ischemia-reperfusion (I/R) and suppressed cardiomyocyte apoptosis, inflammation, and autophagy induced by I/R in rats. Moreover, we confirmed that IIM repressed apoptosis and regulated MMP in H9C2 cells exposed to H/R. IIM relieved the inflammatory response and autophagy in H/R-treated H9C2 cells. In addition, IIM inhibited the Krüpple-like factor 4 (KLF4)/NF-κB pathway in H/R-induced H9C2 cells. Interestingly, the function of IIM on apoptosis, MMP, inflammation and autophagy were abolished by KLF4 overexpression in H/R-induced H9C2 cells. [Conclusions] In conclusion, IIM could repress cardiomyocyte apoptosis, inflammation and autophagy through the inhibition of the KLF4/NF-κB pathway and thus reduced myocardial injury in vivo and in vitro.

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The Novel KLF4/BIG1 Regulates LPS-mediated Neuro-inflammation and Migration in BV2 Cells via PI3K/Akt/NF-kB Signaling Pathway

Cited by 24 publications

References 43 publications

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia

Multitech-Based Study on Medicinal Material Basis and Action Mechanism of Herbal Formula Xian-Ling-Gu-Bao Capsule in Treatment of Osteoarthritis

The protective effect of Iron Isomaltoside on myocardial ischemia-reperfusion injury via the suppression of KLF4/NF-κB signaling

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