CD44 and TGFβ1 synergise to induce expression of a functional NADPH oxidase in promyelocytic cells

Basoni, Caroline; Reuzeau, Edith; Croft, Daniel R.; Génot, Elisabeth; Kramer, IJsbrand M.

doi:10.1016/j.bbrc.2006.03.003

Cited by 7 publications

(5 citation statements)

References 49 publications

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“…HA has been reported to induce ROS in a CD44-dependent manner (94,95), and NOX mediates increases in ROS production (16). Therefore, signaling events that mediate CD44v6 and TGF␤1 are important in lung fibrosis of human subjects (1).…”

Section: Cd44v6 Regulates Tgf␤ri Kinase Activity To Induce Downstreammentioning

confidence: 99%

Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis

Ghatak

Hascall

Markwald

et al. 2017

Journal of Biological Chemistry

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Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of fatal outcome. The lack of information about the signaling pathways that sustain fibrosis and the myofibroblast phenotype has prevented the development of targeted therapies for IPF. Our previous study showed that isolated fibrogenic lung fibroblasts have high endogenous levels of the hyaluronan receptor, CD44V6 (CD44 variant containing exon 6), which enhances the TGFβ1 autocrine signaling and induces fibroblasts to transdifferentiate into myofibroblasts. NADPH oxidase 4 (NOX4) enzyme, which catalyzes the reduction of O to hydrogen peroxide (HO), has been implicated in the cardiac and lung myofibroblast phenotype. However, whether CD44V6 regulates NOX4 to mediate tissue repair and fibrogenesis is not well-defined. The present study assessed the mechanism of how TGF-β-1-induced CD44V6 regulates the NOX4/reactive oxygen species (ROS) signaling that mediates the myofibroblast differentiation. Specifically, we found that NOX4/ROS regulates hyaluronan synthesis and the transcription of via an effect upon activity. Further, CD44V6 is part of a positive-feedback loop with TGFβ1/TGFβRI signaling that acts to increase NOX4/ROS production, which is required for myofibroblast differentiation, myofibroblast differentiation, myofibroblast extracellular matrix production, myofibroblast invasion, and myofibroblast contractility. Both NOX4 and CD44v6 are up-regulated in the lungs of mice subjected to experimental lung injury and in cases of human IPF. Genetic ( shRNA) or a small molecule inhibitor (CD44v6 peptide) targeting of CD44v6 abrogates fibrogenesis in murine models of lung injury. These studies support a function for CD44V6 in lung fibrosis and offer proof of concept for therapeutic targeting of CD44V6 in lung fibrosis disorders.

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Section: Cd44v6 Regulates Tgf␤ri Kinase Activity To Induce Downstreammentioning

confidence: 99%

Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis

Ghatak

Hascall

Markwald

et al. 2017

Journal of Biological Chemistry

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“…Although not regarded as a pro-inflammatory cytokine TGFβ has been implicated in directing the assembly of functional NADPH oxidase on the membrane of premonocytic cells (Basoni et al, 2006).…”

Section: Chemokine Receptorsmentioning

confidence: 99%

Reactive oxygen species (ROS) – a family of fate deciding molecules pivotal in constructive inflammation and wound healing

Bryan

Ahswin²,

Smart³

et al. 2012

eCM

250

164

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Wound healing requires a fine balance between the positive and deleterious effects of reactive oxygen species (ROS); a group of extremely potent molecules, rate limiting in successful tissue regeneration. A balanced ROS response will debride and disinfect a tissue and stimulate healthy tissue turnover; suppressed ROS will result in infection and an elevation in ROS will destroy otherwise healthy stromal tissue. Understanding and anticipating the ROS niche within a tissue will greatly enhance the potential to exogenously augment and manipulate healing. Tissue engineering solutions to augment successful healing and remodelling of wounded or diseased tissue rely on a controlled balance between the constructive and destructive capacity of the leukocyte secretome, including ROS. This review comprehensively considers leukocyte derived ROS in tissue repair with particular interest in surgical intervention with inclusion of a biomaterial. The article considers ROS fundamental chemistry, formation, stimulation and clearance before applying this to discuss the implications of ROS in healing tissue with and without a biomaterial. We also systematically discuss ROS in leukocyte signalling and compare and contrast experimental means of measuring ROS.

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“…3B) or enhanced CD44 expression caused by thrombin pretreatment, or both. HA has been reported to induce ROS production in a CD44-dependent manner (43,60) and NADPH oxidase mediates the increase in ROS production as down-regulation of p47 phox , p67 phox , or Rac1 decreased ROS levels (43). Arterial injury and atherosclerotic lesions are characterized by enhanced thrombin expression and activity (40,41) and increased ROS production in the arteries of apoE…”

mentioning

confidence: 99%

NADPH Oxidases Regulate CD44 and Hyaluronic Acid Expression in Thrombin-treated Vascular Smooth Muscle Cells and in Atherosclerosis

Vendrov

Madamanchi

Niu

et al. 2010

Journal of Biological Chemistry

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Atherosclerosis is a chronic inflammatory disease of the vessel wall in which reactive oxygen species (ROS) 3 -mediated activation of redox-sensitive transcription pathways modulates atherosclerotic plaque progression. Increased adhesion molecule expression and remodeling of extracellular matrix are among the major changes caused by the activation of redoxsensitive signaling pathways. NADPH oxidases are critical determinants of the redox status of the vessel wall and play a critical role in the pathophysiology of atherosclerosis.

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CD44 and TGFβ1 synergise to induce expression of a functional NADPH oxidase in promyelocytic cells

Cited by 7 publications

References 49 publications

Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis

Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis

Reactive oxygen species (ROS) – a family of fate deciding molecules pivotal in constructive inflammation and wound healing

NADPH Oxidases Regulate CD44 and Hyaluronic Acid Expression in Thrombin-treated Vascular Smooth Muscle Cells and in Atherosclerosis

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