Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1

Hong, Chang-Soo; Park, Mi‐Ra; Sun, Eun-Gene; Choi, Wonyoung; Hwang, Jun‐Eul; Bae, Woo-Kyun; Rhee, Joon Haeng; Cho, Sang‐Hee; Chung, Ik‐Joo

doi:10.3389/fimmu.2019.01760

Cited by 27 publications

(28 citation statements)

References 45 publications

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“…This activation seems to be followed by the phosphorylation of IKKβ. Our observations show that TAK1 phosphorylates IKKβ, in accordance with published studies (29). The IKKβ then not only targets the IκB inhibitor protein but also phosphorylates the p65 NF-κB subunit, in agreement with previous observations (30).…”

Section: Discussionsupporting

confidence: 93%

Stromal-Cell-Derived Factor-1(SDF-1) Down-Regulates ANKH via NF-kB Promote Formation of Chondrocyte Mineralization.

Zhu¹,

Liu²,

Tong³

et al. 2021

Preprint

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Osteoarthritis (OA) is one of the most common forms of arthritis. However, the pathogenesis of OA remains unclear. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was associated with some characteristic changes in cartilage. The aim of this study is, therefore, to explore the mechanism of SDF-1 promotes chondrocyte mineralization in OA. The effect of SDF-1 was analyzed with human C-28/I2 chondrocytes. The chondrocytes were transfected with pEX-4-ANKH or siRNA and treated with related inhibitor. The chondrocytes were subjected to Alizarin red S staining, PiPer phosphate assay kit, Alkaline phosphatase staining , RT-PCR and Western blot analysis. In vitro, SDF-1 markedly promoted the mineralization of chondrocytes and suppressed the expression of ANKH, the endogenous mineralization inhibitor. ANKH overexpressed in the chondrocytes significantly decreased the levels of the mineralization in response to SDF-1 treatment. Moreover, SDF-1 promoted an increase in the expression of p-TAK1 and p-IKKβ、p-IkB、p-NF-kB p65. Furthermore, SDF-1 induced decrease in ANKH expression was blocked by IKKβVI (IkB kinase inhibitor). To conclude, SDF-1 suppresses the expression of ANKH via activating NF-kB pathway to aggravate human chondrocytes calcification, suggesting blockade of SDF-1 might be a novel therapy for treatment of OA patients.

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Section: Discussionsupporting

confidence: 93%

Stromal-Cell-Derived Factor-1(SDF-1) Down-Regulates ANKH via NF-kB Promote Formation of Chondrocyte Mineralization.

Zhu¹,

Liu²,

Tong³

et al. 2021

Preprint

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“…Hemopexin can also influence the transformation of the proinflammatory M1 microglia into an anti-inflammatory M2 microglia [93]. The protein Gal-3BP is associated with the immune system [94], as it functions as a suppressor of inflammatory responses by blocking the NF-kB signalling pathway. Remarkably, Gal-3BP can suppress Aβ production through inhibition of the amyloid precursor protein (APP) processing by β-secretase [95].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

Upadhya

Madhu

Attaluri

et al. 2020

J of Extracellular Vesicle

127

145

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Grafting of neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise for brain repair after injury or disease, but safety issues have hindered their clinical application. Employing nano-sized extracellular vesicles (EVs) derived from hiPSC-NSCs appears to be a safer alternative because they likely have similar neuroreparative properties as NSCs and are amenable for non-invasive administration as an autologous or allogeneic off-theshelf product. However, reliable methods for isolation, characterization and testing the biological properties of EVs are critically needed for translation. We investigated signatures of miRNAs and proteins and the biological activity of EVs, isolated from hiPSC-NSCs through a combination of anion-exchange chromatography (AEC) and size-exclusion chromatography (SEC). AEC and SEC facilitated the isolation of EVs with intact ultrastructure and expressing CD9, CD63, CD81, ALIX and TSG 101. Small RNA sequencing, proteomic analysis, pathway analysis and validation of select miRNAs and proteins revealed that EVs were enriched with miRNAs and proteins involved in neuroprotective, anti-apoptotic, antioxidant, anti-inflammatory, blood-brain barrier repairing, neurogenic and Aβ reducing activities. Besides, EVs comprised miRNAs and/or proteins capable of promoting synaptogenesis, synaptic plasticity and better cognitive function. Investigations using an in vitro macrophage assay and a mouse model of status epilepticus confirmed the antiinflammatory activity of EVs. Furthermore, the intranasal administration of EVs resulted in the incorporation of EVs by neurons, microglia and astrocytes in virtually all adult rat and mouse brain regions, and enhancement of hippocampal neurogenesis. Thus, biologically active EVs containing miRNAs and proteins relevant to brain repair could be isolated from hiPSC-NSC cultures, making them a suitable biologic for treating neurodegenerative disorders.

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“…Some of the highly correlated genes (both negative and positive) have been previously reported to participate in viral infection processes. For example, LGALS3BP is a glycoprotein secreted molecule with antiviral properties observed in HIV and Hantavirus infection 33,34 and in the regulation of LPS induced endotoxin shock in murine models 35 . CLIC1 has been previously identified as a virulence factor of Merker Cell Polyomavirus (MCPyV) which is upregulated during infection and promotes the development of Merkel Cell Carcinoma 36 .…”

Section: Resultsmentioning

confidence: 99%

SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity

Alvarez

Sharma

Kee

et al. 2020

Preprint

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COVID-19 outbreak is the biggest threat to human health in recent history. Currently, there are over 1.5 million related deaths and 75 million people infected around the world (as of 22/12/2020). The identification of virulence factors which determine disease susceptibility and severity in different cell types remains an essential challenge. The serine protease TMPRSS2 has been shown to be important for S protein priming and viral entry, however, little is known about its regulation. SPINT2 is a member of the family of Kunitz type serine protease inhibitors and has been shown to inhibit TMPRSS2. Here, we explored the existence of a co-regulation between SPINT2/TMPRSS2 and found a tightly regulated protease/inhibitor expression balance across tissues. We found that SPINT2 negatively correlates with SARS-CoV-2 expression in Calu-3 and Caco-2 cell lines and was down-regulated in secretory cells from COVID-19 patients. We validated our findings using Calu-3 cell lines and observed a strong increase in viral load after SPINT2 knockdown. Additionally, we evaluated the expression of SPINT2 in datasets from comorbid diseases using bulk and scRNA-seq data. We observed its down-regulation in colon, kidney and liver tumors as well as in alpha pancreatic islets cells from diabetes Type 2 patients, which could have implications for the observed comorbidities in COVID-19 patients suffering from chronic diseases.

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Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1

Cited by 27 publications

References 45 publications

Stromal-Cell-Derived Factor-1(SDF-1) Down-Regulates ANKH via NF-kB Promote Formation of Chondrocyte Mineralization.

Stromal-Cell-Derived Factor-1(SDF-1) Down-Regulates ANKH via NF-kB Promote Formation of Chondrocyte Mineralization.

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity

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