Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Mouse Model of Glaucoma Filtration Surgery and TGFβ1-Induced Responses in Human Tenon's Fibroblasts.

Purpose: Cytotoxic agents such as mitomycin C (MMC) are part of the mainstay treatment for limiting subconjunctival scarring following glaucoma filtration surgery (GFS). However, a safer antifibrotic therapy is clinically needed. The anti-scarring properties of 3',4'-dihydroxyflavonol (DiOHF) were evaluated in a mouse model of GFS and in cultured human Tenon's fibroblasts (HTFs).

Nox4 Facilitates TGFβ1-Induced Fibrotic Response in Human Tenon's Fibroblasts and Promotes Wound Collagen Accumulation in Murine Model of Glaucoma Filtration Surgery.

Collagen accumulation in sub-conjunctival tissue at the surgical wound is one of the major complications associated with glaucoma filtration surgery (GFS). This process often leads to unwanted fibrotic scar formation at the lesion site and dysfunction of tissues. Previously, we demonstrated that NADPH oxidase 4 (Nox4) is implicated in transforming growth factor-beta (TGFβ)-induced collagen production in ocular fibroblasts and scarring responses in a mouse model of corneal injury.

Wound Healing After Alkali Burn Injury of the Cornea Involves Nox4-Type NADPH Oxidase.

Purpose: Corneal injury that occurs after burning with alkali initiates wound-healing processes, including inflammation, neovascularization, and fibrosis. Excessive reactions to injury can reduce corneal transparency and thereby compromise vision. The NADPH oxidase (Nox) enzyme complex is known to be involved in cell signaling for wound-healing angiogenesis, but its role in corneal neovascularization has been little studied.

Transforming Growth Factor β1-Induced NADPH Oxidase-4 Expression and Fibrotic Response in Conjunctival Fibroblasts.

Purpose: Fibrotic scarring after ocular surgeries and chemical burn injuries can impede clarity of the cornea and cause vision impairment. Transforming growth factor β (TGFβ) signaling pathway is known to mediate fibrotic scarring, and NADPH oxidase-derived reactive oxygen species has been shown to be an effector molecule that facilitates TGFβ1-mediated responses. The present study explores the expression profile and functional importance of NADPH oxidase (Nox) in conjunctival fibroblasts.

Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells.

Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (HO) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood.

miRNA involvement in angiogenesis in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Late-stage AMD is characterized by choroidal neovascularization (CNV). miR-93 appears to play a role in regulating vascular endothelial growth factor-A (VEGF-A), a known factor involved in neovascularization.

miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model.

miR-126 has recently been implicated in modulating angiogenic factors in vascular development. Understandings its biological significance might enable development of therapeutic interventions for diseases like age-related macular degeneration (AMD). We aimed to determine the role of miR-126 in AMD using a laser-induced choroidal neovascularization (CNV) mouse model.

Trichostatin A, a histone deacetylase inhibitor suppresses NADPH Oxidase 4-Derived Redox Signalling and Angiogenesis.

Histone deacetylase (HDAC) inhibitors are known to suppress abnormal development of blood vessels. Angiogenic activity in endothelial cells depends upon NADPH oxidase 4 (Nox4)-dependent redox signalling. We set out to study whether the HDAC inhibitor trichostatin A (TSA) affects Nox4 expression and angiogenesis.

NADPH oxidase 2 plays a role in experimental corneal neovascularization.

Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied.

Differential effects of superoxide dismutase and superoxide dismutase/catalase mimetics on human breast cancer cells.

Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) have been implicated in development and progression of breast cancer. In the present study, we have evaluated the effects of the superoxide dismutase (SOD) mimetic MnTmPyP and the SOD/catalase mimetic EUK 134 on superoxide and H2O2 formation as well as proliferation, adhesion, and migration of MCF-7 and MDA-MB-231 cells. Superoxide and H2O2 production was examined using dihydroethidium and Amplex red assays, respectively.

Smad-independent pathway involved in transforming growth factor β1-induced Nox4 expression and proliferation of endothelial cells.

NADPH oxidase-derived reactive oxygen species are important for various cellular functions, including proliferation. Endothelial cells predominantly express the Nox4 isoform of NADPH oxidase, but it is not entirely clear how it is regulated. In this study, we investigated the signalling pathways involved in transforming growth factor-β1 (TGF-β1)-induced Nox4 expression and the proliferation of human microvascular endothelial cells (HMECs).

Transforming growth factor-β1 requires NADPH oxidase 4 for angiogenesis in vitro and in vivo.

Angiogenesis, the formation of new blood vessels, is a key physiological event in organ development and tissue responses to hypoxia but is also involved in pathophysiologies such as tumour growth and retinopathies. Understanding the molecular mechanisms involved is important to design strategies for therapeutic intervention. One important regulator of angiogenesis is transforming growth factor-β1 (TGF-β1).

Prostacyclin signaling boosts NADPH oxidase 4 in the endothelium promoting cytoprotection and angiogenesis.

Aims: Prostacyclin (PGI2) that is released from the vascular endothelium plays an important role in vasodilatation and thrombo-resistance, and it has long been suspected to protect cell survival. How it does so has never been clear. Recently, it has been shown that the NADPH oxidase 4 (Nox4) improves endothelial cell functions and promotes angiogenesis in vivo, but it was not known how to boost Nox4 therapeutically to exploit its protective functions in the vasculature.

Involvement of Nox2 NADPH oxidase in retinal neovascularization.

Purpose: The proliferation of new blood vessels in the retina is a leading cause of vision impairment. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) is involved in cell signaling for ischemia-induced angiogenesis, but its role in retinal neovascularization is unclear. We have analyzed the dependence of retinal neovascularization on the Nox2 isoform in oxygen-induced retinopathy (OIR) in mice.

Pharmacological priming of adipose-derived stem cells for paracrine VEGF production with deferoxamine.

Adipose-derived stem cells (ASCs) show great potentials in applications such as therapeutic angiogenesis, regenerative medicine and tissue engineering. Pharmacological preconditioning of stem cells to boost the release of cytoprotective factors may represent an effective way to enhance their therapeutic efficacy. In this study, the aim was to determine whether deferoxamine can enhance the release of vascular endothelial growth factor (VEGF) from in vitro expanded ASCs.

Annexin peptide Ac2-26 suppresses TNFα-induced inflammatory responses via inhibition of Rac1-dependent NADPH oxidase in human endothelial cells.

The anti-inflammatory peptide annexin-1 binds to formyl peptide receptors (FPR) but little is known about its mechanism of action in the vasculature. Here we investigate the effect of annexin peptide Ac2-26 on NADPH oxidase activity induced by tumour necrosis factor alpha (TNFα) in human endothelial cells. Superoxide release and intracellular reactive oxygen species (ROS) production from NADPH oxidase was measured with lucigenin-enhanced chemiluminescence and 2',7'-dichlorodihydrofluorescein diacetate, respectively.

Hypoxic conditioning enhances the angiogenic paracrine activity of human adipose-derived stem cells.

Human adipose-derived stem cells (ASCs) secrete cytokines and growth factors that can be harnessed in a paracrine fashion for promotion of angiogenesis, cell survival, and activation of endogenous stem cells. We recently showed that hypoxia is a powerful stimulus for an angiogenic activity from ASCs in vitro and here we investigate the biological significance of this paracrine activity in an in vivo angiogenesis model. A single in vitro exposure of ASCs to severe hypoxia (<0.

Nox4 modulates collagen production stimulated by transforming growth factor β1 in vivo and in vitro.

The synthesis of extracellular matrix including collagen during wound healing responses involves signaling via reactive oxygen species (ROS). We hypothesized that NADPH oxidase isoform Nox4 facilitates the stimulatory effects of the profibrotic cytokine transforming growth factor (TGF) β(1) on collagen production in vitro and in vivo. TGFβ(1) stimulated collagen synthesis and hydrogen peroxide generation in mouse cardiac fibroblasts, and both responses were attenuated by a scavenger of superoxide and hydrogen peroxide (EUK-134).

Differentiation of human adipose-derived stem cells into fat involves reactive oxygen species and Forkhead box O1 mediated upregulation of antioxidant enzymes.

Both reactive oxygen species (ROS) and Forkhead box O (FOXO) family transcription factors are involved in the regulation of adipogenic differentiation of preadipocytes and stem cells. While FOXO has a pivotal role in maintaining cellular redox homeostasis, the interactions between ROS and FOXO during adipogenesis are not clear. Here we examined how ROS and FOXO regulate adipogenesis in human adipose-derived stem cells (hASC).

Microphthalmia-associated transcription factor modulates expression of NADPH oxidase type 4: a negative regulator of melanogenesis.

How signaling via reactive oxygen species (ROS) influences skin pigmentation is unclear. We have investigated how NADPH oxidase-derived ROS modulates the expression of the key pigment "melanin" synthesizing enzymes in B16 mouse melanoma cells. A melanin inducer α-melanocyte-stimulating hormone (α-MSH) caused ROS generation that was inhibited by the NADPH oxidase inhibitor Diphenyleneiodonium (DPI) and was insensitive to antagonists of other ROS-producing enzyme systems including mitochondrial enzymes, cycloxygenase, and xanthine oxidase.

Hypoxic preconditioning enhances survival of human adipose-derived stem cells and conditions endothelial cells in vitro.

To grow more robust cardiac tissue for implantation in vivo, strategies to improve survival of implanted stem cells are required. Here we report the protective effects of hypoxic preconditioning (HPC) and identify mechanisms for improving survival of adipose-derived stem cells (ASC) in vitro. Human ASC were preconditioned for 24 h with hypoxia and then exposed to simulated ischemia for a further 24 h.

Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation.

Cardiac fibrosis is a consequence of many cardiovascular diseases and contributes to impaired ventricular function. Activation of the prostacyclin receptor (IP) protects against cardiac fibrosis, but the molecular mechanisms are not totally understood. Using mouse cardiac fibroblasts, we found that IP activation with cicaprost suppressed expression of collagen I and other target genes of transforming growth factor-beta.

Reconstituted high-density lipoprotein suppresses leukocyte NADPH oxidase activation by disrupting lipid rafts.

Reconstituted discoidal high-density lipoprotein (rHDL) has potent vascular protective actions. Native HDL suppresses cellular generation of reactive oxygen species, whereas this antioxidant effect of rHDL is less clear. This study examined the effects of rHDL on NADPH oxidase, a major source of cellular superoxide generation, in both leukocytes and human umbilical vein endothelial cells.