NOX1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset IBD and NOX1 Deficiency

Khoshnevisan, Razieh; Anderson, Michael J.; Babcock, Stephen; Anderson, Sierra; Illig, David W.; Marquardt, Benjamin; Sherkat, Roya; Schröder, Katrin; Moll, Franziska; Hollizeck, Sebastian; Rohlfs, Meino; Walz, Christoph; Adibi, Peyman; Rezaei, Abbas; Andalib, Alireza; Koletzko, Sibylle; Muise, Aleixo M.; Snapper, Scott B.; Klein, Christoph; Thiagarajah, Jay R.; Kotlarz, Daniel

doi:10.1093/ibd/izaa017

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…This result is consistent with a study performed in our lab, where we provide evidence that loss of NoxO1 in mice results in less differentiation of enterocytes and spurs DSS/AOM induced colitis and cancer formation [8]. In contrast, inflammatory bowl disease is associated with TNFα/NFκB induced expression of NoxO1 and increased Nox1 derived ROS formation [9,10]. In stomach, NoxO1 potentially has pro-tumorigenic functions.…”

Section: Introductionsupporting

confidence: 92%

NoxO1 Determines Level of ROS Formation by the Nox1 Centered NADPH Oxidase

Hebchen¹,

Spaeth²,

Müller³

et al. 2023

Preprint

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Activity of the Nox1 centered NADPH oxidase complex depends on the activator NoxA1 and the organizer NoxO1. NoxO1 itself is not involved in electron transfer for superoxide formation. Instead, by creating proximity of all components in the right place NoxO1 enables a constitutive formation of reactive oxygen species by that complex. All subunits should form the complex in a 1:1:1 ratio. When analyzing different cell lines in this study, we found an unequal expression of the component on mRNA level with an excess of NoxO1. Even with plasmid-based overexpression of individual components of Nox1 centered NADPH oxidase complex results in different expression of their mRNA, with NoxO1 mRNA being best expressed. Despite an unchanged high level of NoxO1 mRNA over a wide range of transfected plasmid, protein expression is increased with accelerating plasmid concentrations. We thought to analyze the ability of NoxO1 to induce ROS formation, when present in different ratio to Nox1 and NoxA1. To this end, we used Hek293 cells with constitutive expression of Nox1 and NoxA1 transfected with increasing concentrations of NoxO1. Our results suggest that ROS formation by the Nox1 centered NADPH oxidase strongly depends on the level of NoxO1 and a surplus of NoxO1 further increases the activity of the complex.

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Section: Introductionsupporting

confidence: 92%

NoxO1 Determines Level of ROS Formation by the Nox1 Centered NADPH Oxidase

Hebchen¹,

Spaeth²,

Müller³

et al. 2023

Preprint

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“…During inflammation of the lung caused by the influenza A virus, NOX1 suppresses inflammation and oxidative stress, and on the contrary, the NOX2 isoform seems to have a pro-inflammatory role in the regulation of influenza A infections ( Selemidis et al, 2013 ). In IBD, it was recently demonstrated that a lowered ROS-production in cells due to the loss of NOX1 is associated with delayed wound healing, cytoskeletal changes, and altered collective cell migration, which affect tissue repair and barrier function ( Khoshnevisan et al, 2020 ). Human bronchial epithelial (NHBE) cells express HYAL2 (hyaluronidase 2), a hyaluronan-degrading enzyme, and ROS increases HYAL2 activity and expression.…”

Section: Discussionmentioning

confidence: 99%

Theoretical Analysis of S, M and N Structural Proteins by the Protein–RNA Recognition Code Leads to Genes/proteins that Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis

Nahálka

2021

Front. Genet.

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In this conceptual review, based on the protein–RNA recognition code, some theoretical sequences were detected in the spike (S), membrane (M) and capsid (N) proteins that may post-transcriptionally regulate the host genes/proteins in immune homeostasis, pulmonary epithelial tissue homeostasis, and lipid homeostasis. According to the review of literature, the spectrum of identified genes/proteins shows that the virus promotes IL1α/β–IL1R1 signaling (type 1 immunity) and immunity defense against helminths and venoms (type 2 immunity). In the alteration of homeostasis in the pulmonary epithelial tissue, the virus blocks the function of cilia and the molecular programs that are involved in wound healing (EMT and MET). Additionally, the protein–RNA recognition method described here identifies compatible sequences in the S1A-domain for the post-transcriptional promotion of PIKFYVE, which is one of the critical factors for SARS-CoV-2 entry to the host cell, and for the post-transcriptional repression of xylulokinase XYLB. A decrease in XYLB product (Xu5P) in plasma was proposed as one of the potential metabolomics biomarkers of COVID-19. In summary, the protein–RNA recognition code leads to protein genes relevant to the SARS-CoV-2 life cycle and pathogenesis.

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“…ROS produced by epithelial NOX1 contribute to the proliferation and differentiation of colonic epithelial cells by modulating the PI3K/AKT/Wnt and Notch1 signaling pathways (Coant et al, 2010). Furthermore, NOX1-mediated cellular ROS production is required for collective migration of epithelial cells, because defective directional migration and altered cell-cell contact were observed in cells with loss of NOX1 function (Khoshnevisan et al, 2020). Intestinal epithelial cells cover the outermost surface of the mucosa and interface with the lamina propria to form the intestinal mucosal barrier (Quiros and Nusrat, 2019).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function

et al. 2020

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Disturbance of epithelial barrier function causes chronic intestinal inflammation such as inflammatory bowel disease. Several studies have reported that Th2 cytokines such as interleukin (IL)-4 and IL-13 play an important role in the regulation of intestinal barrier function. However, the precise role of the IL-4 receptor α subunit (IL-4Rα) in intestinal inflammation remains unclear. Thus, we used an experimental colitis model to investigate the role of IL-4Rα in intestinal inflammation. IL-4Rα-deficient (IL-4Rα-/-) mice and their littermate wild-type (WT) mice were used. Experimental colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water for seven days. Treatment with DSS caused body weight loss, an increase in the disease activity index and histological abnormalities in WT colitis mice, all of which were significantly attenuated in IL-4Rα-/-colitis mice. Neutrophil infiltration in the colonic mucosa was reduced in IL-4Rα-/-colitis mice compared with WT colitis mice. NADPH oxidase 1 expression and reactive oxygen species production were increased in the colons of IL-4Rα-/-mice. Furthermore, elevated intestinal permeability induced by DSS treatment was suppressed in IL-4Rα-/-colitis mice. These results demonstrate that IL-4Rα-/-mice exhibit reduced susceptibility to DSS-induced colitis. Our present findings suggest that IL-4Rα deficiency enhances intestinal mucosal barrier function through the upregulation of NADPH oxidase 1-dependent reactive oxygen species production, thereby suppressing the development of intestinal inflammation.

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NOX1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset IBD and NOX1 Deficiency

Cited by 10 publications

References 39 publications

NoxO1 Determines Level of ROS Formation by the Nox1 Centered NADPH Oxidase

NoxO1 Determines Level of ROS Formation by the Nox1 Centered NADPH Oxidase

Theoretical Analysis of S, M and N Structural Proteins by the Protein–RNA Recognition Code Leads to Genes/proteins that Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis

Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function

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