12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3

Blažević, Tina; Schwaiberger, Andrea V.; Schreiner, Cornelia E.; Schachner, Daniel; Schaible, Anja; Grojer, Christoph S.; Atanasov, Atanas G.; Werz, Oliver; Dirsch, Verena M.; Heiss, Elke H.

doi:10.1074/jbc.m113.489013

Cited by 28 publications

(26 citation statements)

References 53 publications

(64 reference statements)

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“…The PDGF receptor (PDGFR) is classified as a receptor tyrosine kinase, and two receptor types (i.e., PDGFR‐α and PDGFR‐β) have been identified to date . Upon activation, PDGFRs dimerize, and are auto‐phosphorylated on their cytosolic domains, which subsequently activate signal transduction through the PI3K pathway or through the generation of reactive oxygen species (ROS) . PDGF‐C and D have recently been identified, and PDGF‐D mediates its function through PDGFR‐β .…”

Section: Introductionmentioning

confidence: 99%

Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

et al. 2015

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Platelet-derived growth factor-D (PDGF-D) was recently identified, and acts as potent mitogen for mesenchymal cells. PDGF-D also induces cellular transformation and promotes tumor growth. However, the functional role of PDGF-D in adipose-derived stem cells (ASCs) has not been identified. Therefore, we primarily investigated the autocrine and paracrine roles of PDGF-D in this study. Furthermore, we identified the signaling pathways and the molecular mechanisms involved in PDGF-D-induced stimulation of ASCs. It is of interest that PDGF-B is not expressed, but PDGF-D and PDGF receptor-b are expressed in ASCs. PDGF-D showed the strongest mitogenic effect on ASCs, and PDGF-D regulates the proliferation and migration of ASCs through the PI3K/Akt pathways. PDGF-D also increases the proliferation and migration of ASCs through generation of mitochondrial reactive oxygen species (mtROS) and mitochondrial fission. mtROS generation and fission were mediated by p66Shc phosphorylation, and BCL2-related protein A1 and Serpine peptidase inhibitor, clade E, member 1 mediated the proliferation and migration of ASCs. In addition, PDGF-D upregulated the mRNA expression of diverse growth factors such as vascular endothelial growth factor A, fibroblast growth factor 1 (FGF1), FGF5, leukemia inhibitory factor, inhibin, beta A, interleukin 11, and heparin-binding EGF-like growth factor. Therefore, the preconditioning of PDGF-D enhanced the hair-regenerative potential of ASCs. PDGF-D-induced growth factor expression was attenuated by a pharmacological inhibitor of mitogen-activated protein kinase pathway. In summary, PDGF-D is highly expressed by ASCs, where it acts as a potent mitogenic factor. PDGF-D also upregulates growth factor expression in ASCs. Therefore, PDGF-D can be considered a novel ASC stimulator, and used as a preconditioning agent before ASC transplantation. STEM CELLS 2015;33:542-556

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Section: Introductionmentioning

confidence: 99%

Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

et al. 2015

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“…The first group of pathways such as IL6, CCR5, PDGF, and EGF showed peak in their activity between 2 and 4 hours after infection. Activation of PDGF pathway leads to induction of several signal transduction pathways through the PI3K pathway or through reactive oxygen species-mediated activation of the STAT3 pathway [ 31 ]. Downstream effects of this include regulation of the cell cycle and cell migration [ 32 ] which are critical in generating adaptive immune response initiated by DCs.…”

Section: Resultsmentioning

confidence: 99%

Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

Anderson

DeDiego

Topham

et al. 2016

Computational and Mathematical Methods in Medicine

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Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

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“…ROS activate EGF signaling pathways, which accelerates re-epithelialization of wounds by the migration and proliferation of keratinocytes (50,51). Similarly, activation of PDGF is also mediated by ROS through the STAT3 signaling pathway (52). However, further studies are necessary to understand the delicate balance between ROS release and the production of growth factors, because exacerbated ROS levels can affect the migration and proliferation of fibroblasts and impair wound healing (53).…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

Montoya

Daza

Muñoz

et al. 2015

Antimicrob Agents Chemother

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An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm 2 , 15 min), twice a week for 3 weeks. Cutaneous leishmaniasis (CL) is a parasitic disease caused by protozoa of the genus Leishmania, which manifests as a chronic infection affecting mainly mononuclear phagocytes of the skin (1). The disease affects the poorest populations in 99 countries in tropical and subtropical regions of the world (2, 3). It is estimated that 14 million people are infected, 350 million are at risk, and there are about 1.5 million new cases per year (3, 4). The parasite is transmitted by the bite of an insect vector belonging to the genus Lutzomyia (in America) or Phlebotomus (in Europe, Asia, and Africa) in the subfamily Phlebotominae (5).Only three types of drugs are available to treat CL. They are the pentavalent antimonials (meglumine antimoniate and sodium stibogluconate), pentamidine isethionate, and miltefosine. Miltefosine is the only one available for oral administration (4). These medications are delivered at high doses and for long periods, thus leading to high toxicity. Therefore, their use is contraindicated in pregnant women, in patients with cardiovascular, renal, or hepatic disease, and in children with low body weight (6). Overall, the efficacy of these drugs varies between 55 and 98% depending on the compound and on the Leishmania species causing the clinical manifestation (7,8). However, their elevated toxicity encourages abandonment of treatment and consequently a decrease in the efficacy (9).More recently, photodynamic therapy (PDT) has emerged as an alternative to treat CL (10). This therapy is based on the application of a photosensitizing agent (PA) that, when excited by light of a certain wavelength, induces the production of reactive oxygen species (ROS) that can destroy the microorganism or the target cell (11). In spite of its potential, only a few PAs have been tested against CL in animal models, and only one in humans. Topical application of 5-aminolevulinic acid (ALA) and light in a murine model of CL caused by L. major showed a significant reduction of the parasitic load and the size of lesions (12). Intralesional administration of ALA (one to three PDT sessions) in a patient with CL by L. major produced a 10 to 20% cure, although it is probable that clinical outcome resulted from nonspecific destruction of infected macrophages instead of...

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12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of Transcription 3

Cited by 28 publications

References 53 publications

Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

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