Farhat, Katja

[["dc.bibliographiccitation.firstpage","33756"],["dc.bibliographiccitation.issue","44"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","33763"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Le-Huu, Sinja"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T08:37:53Z"],["dc.date.available","2018-11-07T08:37:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Cells are responding to hypoxia via prolyl-4-hydroxylase domain (PHD) enzymes, which are responsible for oxygen-dependent hydroxylation of the hypoxia-inducible factor (HIF)-1 alpha subunit. To gain further insight into PHD function, we generated knockdown cell models for the PHD2 isoform, which is the main isoform regulating HIF-1 alpha hydroxylation and thus stability in normoxia. Induction of a PHD2 knockdown in tetracycline-inducible HeLa PHD2 knockdown cells resulted in increased F-actin formation as detected by phalloidin staining. A similar effect could be observed in the stably transfected PHD2 knockdown cell clones 1B6 and 3B7. F-actin is at least in part responsible for shaping cell morphology as well as regulating cell migration. Cell migration was impaired significantly as a consequence of PHD2 knockdown in a scratch assay. Mechanistically, PHD2 knockdown resulted in activation of the RhoA (Ras homolog gene family member A)/Rho-associated kinase pathway with subsequent phosphorylation of cofilin. Because cofilin phosphorylation impairs its actin-severing function, this may explain the F-actin phenotype, thereby providing a functional link between PHD2-dependent signaling and cell motility."],["dc.identifier.doi","10.1074/jbc.M110.132985"],["dc.identifier.isi","000283354000021"],["dc.identifier.pmid","20801873"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18648"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin Phosphorylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1331"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1346"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, Michaela"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:21:57Z"],["dc.date.available","2018-11-07T09:21:57Z"],["dc.date.issued","2013"],["dc.description.abstract","The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. GLIA 2013;61:1331-1346"],["dc.identifier.doi","10.1002/glia.22518"],["dc.identifier.isi","000321983400011"],["dc.identifier.pmid","23832647"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29226"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Carcinoma cells misuse the host tissue damage response to invade the brain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e18605"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Deng, Ying"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Oberland, Sonja"],["dc.contributor.author","Gisselmann, Guenter"],["dc.contributor.author","Neuhaus, Eva M."],["dc.date.accessioned","2018-11-07T08:57:06Z"],["dc.date.available","2018-11-07T08:57:06Z"],["dc.date.issued","2011"],["dc.description.abstract","Seven-transmembrane receptors typically mediate olfactory signal transduction by coupling to G-proteins. Although insect odorant receptors have seven transmembrane domains like G-protein coupled receptors, they have an inverted membrane topology, constituting a key difference between the olfactory systems of insects and other animals. While heteromeric insect ORs form ligand-activated non-selective cation channels in recombinant expression systems, the evidence for an involvement of cyclic nucleotides and G-proteins in odor reception is inconsistent. We addressed this question in vivo by analyzing the role of G-proteins in olfactory signaling using electrophysiological recordings. We found that G alpha(s) plays a crucial role for odorant induced signal transduction in OR83b expressing olfactory sensory neurons, but not in neurons expressing CO2 responsive proteins GR21a/GR63a. Moreover, signaling of Drosophila ORs involved G alpha(s) also in a heterologous expression system. In agreement with these observations was the finding that elevated levels of cAMP result in increased firing rates, demonstrating the existence of a cAMP dependent excitatory signaling pathway in the sensory neurons. Together, we provide evidence that G alpha(s) plays a role in the OR mediated signaling cascade in Drosophila."],["dc.description.sponsorship","NE [755/3-1]; Max-Planck-Research School for Chemical Biology (IMPRS-CB)"],["dc.identifier.doi","10.1371/journal.pone.0018605"],["dc.identifier.isi","000289238700028"],["dc.identifier.pmid","21490930"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8314"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23308"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Stimulatory G alpha(s) Protein Is Involved in Olfactory Signal Transduction in Drosophila"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","365"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Leukocyte Biology"],["dc.bibliographiccitation.lastpage","375"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Swain, Lija"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Hillemann, Annette"],["dc.contributor.author","Beneke, Angelika"],["dc.contributor.author","Odagiri, Haruki"],["dc.contributor.author","Terada, Kazutoyo"],["dc.contributor.author","Endo, Motoyoshi"],["dc.contributor.author","Oike, Yuichi"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:36:09Z"],["dc.date.available","2018-11-07T09:36:09Z"],["dc.date.issued","2014"],["dc.description.abstract","On a molecular level, cells sense changes in oxygen availability through the PHDs, which regulate the protein stability of the alpha-subunit of the transcription factor HIF. Especially, PHD3 has been additionally associated with apoptotic cell death. We hypothesized that PHD3 plays a role in cell-fate decisions in macrophages. Therefore, myeloid-specific PHD3(-/-) mice were created and analyzed. PHD3(-/-) BMDM showed no altered HIF-1 alpha or HIF-2 alpha stabilization or increased HIF target gene expression in normoxia or hypoxia. Macrophage M1 and M2 polarization was unchanged likewise. Compared with macrophages from WT littermates, PHD3(-/-) BMDM exhibited a significant reduction in TUNEL-positive cells after serum withdrawal or treatment with stauro and SNAP. Under the same conditions, PHD3(-/-) BMDM also showed less Annexin V staining, which is representative for membrane disruption, and indicated a reduced early apoptosis. In an unbiased transcriptome screen, we found that Angptl2 expression was reduced in PHD3(-/-) BMDM under stress conditions. Addition of rAngptl2 rescued the antiapoptotic phenotype, demonstrating that it is involved in the PHD3-mediated response toward apoptotic stimuli in macrophages."],["dc.identifier.doi","10.1189/jlb.2HI1013-533R"],["dc.identifier.isi","000340829400003"],["dc.identifier.pmid","24626957"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32548"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1938-3673"],["dc.relation.issn","0741-5400"],["dc.title","Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2787"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","2798"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Bordoli, Mattia Renato"],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Kristiansen, Glen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T09:23:40Z"],["dc.date.available","2018-11-07T09:23:40Z"],["dc.date.issued","2013"],["dc.description.abstract","The prolyl-4-hydroxylase domain 13 (PHD13) enzymes are regulating the protein stability of the -subunit of the hypoxia-inducible factor-1 (HIF-1), which mediates oxygen-dependent gene expression. PHD2 is the main isoform regulating HIF-1 hydroxylation and thus stability in normoxia. In human cancers, HIF-1 is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA-MB-231 breast cancer cells and analyzed their tumor-forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA-MB-231 cells, which could be partially rescued by re-establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA-MB-231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)-1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro-protein convertase furin. Thus, our data demonstrate that in MDA-MB-231 cells PHD2 might affect tumor-relevant TGF-1 target gene expression by altering the TGF-1 processing capacity."],["dc.description.sponsorship","Wilhelm Sander Stiftung [1348530]"],["dc.identifier.doi","10.1002/ijc.27982"],["dc.identifier.isi","000317593100008"],["dc.identifier.pmid","23225569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29634"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0020-7136"],["dc.title","Knockdown of prolyl-4-hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA-MB-231 cells by affecting TGF-1 processing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e69128"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T09:22:20Z"],["dc.date.available","2018-11-07T09:22:20Z"],["dc.date.issued","2013"],["dc.description.abstract","Cells can adapt to hypoxia by various mechanisms. Yet, hypoxia-induced effects on the cytoskeleton-based cell architecture and functions are largely unknown. Here we present a comprehensive analysis of the architecture and function of L929 fibroblasts under hypoxic conditions (1% O-2). Cells cultivated in hypoxia showed striking morphological differences as compared to cells cultivated under normoxic conditions (20% O-2). These changes include an enlargement of cell area and volume, increased numbers of focal contacts and loss of cell polarization. Furthermore the beta- and gamma-actin distribution is greatly altered. These hypoxic adjustments are associated with enhanced cell spreading and a decline of cell motility in wound closure and single cell motility assays. As the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is stabilised in hypoxia and plays a pivotal role in the transcriptional response to changes in oxygen availability we used an shRNA-approach to examine the role of HIF-1 alpha in cytoskeleton-related architecture and functions. We show that the observed increase in cell area, actin filament rearrangement, decrease of single cell migration in hypoxia and the maintenance of p-cofilin levels is dependent on HIF-1 alpha stabilisation."],["dc.identifier.doi","10.1371/journal.pone.0069128"],["dc.identifier.isi","000324146200061"],["dc.identifier.pmid","23874890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hypoxia Modulates Fibroblastic Architecture, Adhesion and Migration: A Role for HIF-1 alpha in Cofilin Regulation and Cytoplasmic Actin Distribution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","77"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","86"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hoelscher, Marion"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Hesse, Amke"],["dc.contributor.author","Silter, Monique"],["dc.contributor.author","Lin, Yun"],["dc.contributor.author","Pichler, Bernd J."],["dc.contributor.author","Thistlethwaite, Patricia"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T09:11:48Z"],["dc.date.available","2018-11-07T09:11:48Z"],["dc.date.issued","2012"],["dc.description.abstract","The hypoxia-inducible factor-1 (HIF-1) is the master modulator of hypoxic gene expression. The effects of chronically stabilized cardiac HIF-1 and its role in the diseased heart are not precisely known. The aims of this study were as follows: (i)to elucidate consequences of HIF-1 stabilization in the heart; (ii)to analyse long-term effects of HIF-1 stabilization with ageing and the ability of the HIF-1 overexpressing hearts to respond to increased mechanical load; and (iii)to analyse HIF-1 protein levels in failing heart samples. In a cardiac-specific HIF-1 transgenic mouse model, constitutive expression of HIF-1 leads to changes in capillary area and shifts the cardiac metabolism towards glycolysis with a net increase in glucose uptake. Furthermore, Ca-2 handling is altered, with increased Ca-2 transients and faster intracellular [Ca-2] decline. These changes are associated with decreased expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a but elevated phosphorylation of phospholamban. HIF-1 transgenic mice subjected to transverse aortic constriction exhibited profound cardiac decompensation. Moreover, cardiomyopathy was also seen in ageing transgenic mice. In parallel, we found an increased stabilization of HIF-1 in heart samples of patients with end-stage heart failure. Changes induced with transgenic cardiac HIF-1 possibly mediate beneficial effects in the short term; however, with increased mechanical load and ageing they become detrimental for cardiac function. Together with the finding of increased HIF-1 protein levels in samples from human patients with cardiomyopathy, these data indicate that chronic HIF-1 stabilization drives autonomous pathways that add to disease progression."],["dc.identifier.doi","10.1093/cvr/cvs014"],["dc.identifier.isi","000301983100012"],["dc.identifier.pmid","22258630"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26804"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0008-6363"],["dc.title","Unfavourable consequences of chronic cardiac HIF-1 stabilization"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","107"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell and tissue research"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","343"],["dc.contributor.author","Jungi, Thomas W"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Burgener, Iwan A"],["dc.contributor.author","Werling, Dirk"],["dc.date.accessioned","2019-07-09T11:53:48Z"],["dc.date.available","2019-07-09T11:53:48Z"],["dc.date.issued","2011"],["dc.description.abstract","Toll-like receptors are pattern recognition receptors with which hosts recognize pathogen-associated molecular patterns (PAMP). This recognition process is translated rapidly into a meaningful defense reaction. This form of innate host defense is preserved in the animal kingdom: invertebrates heavily depend on it; higher vertebrates also have an adaptive immune system. Both adaptive and innate immune systems are intertwined in that the former also depends on an intact innate recognition and response system. Members of the TLR system cover recognition of parasitic, bacterial or viral germs. Due to the constraints imposed by the necessity to recognize PAMP and to interact with downstream signaling molecules, the TLR system is relatively conserved in evolution. Nevertheless, subtle species differences have been reported for several mammalian TLR members. Examples of this will be given. In all mammalian species investigated, part of the coding sequence is available for the most important TLR members, thus allowing study of expression of these TLR members in various tissues by reverse-transcription polymerase chain reaction in its classical (RT-PCR) and quantitative real time RT-PCR (qRT-PCR) form. In some species, the whole coding sequences of the most important or even all TLR members are known. This allows construction of cDNA and transfection of common host cells, thus permitting functional studies. Extensive investigations were devoted to the study of non-synonymous single nucleotide polymorphisms. In a few cases, expression of a given amino acid in the extracellular (ligand-binding) portion of TLR members could be associated with infectious diseases. This will be discussed below."],["dc.identifier.doi","10.1007/s00441-010-1047-8"],["dc.identifier.fs","584201"],["dc.identifier.pmid","20927536"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60498"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-0878"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.mesh","Animal Diseases"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Animals, Domestic"],["dc.subject.mesh","Bacteria"],["dc.subject.mesh","Signal Transduction"],["dc.subject.mesh","Species Specificity"],["dc.subject.mesh","Toll-Like Receptors"],["dc.title","Toll-like receptors in domestic animals."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3426"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","3438"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Kalucka, Joanna"],["dc.contributor.author","Ettinger, Andreas"],["dc.contributor.author","Franke, Kristin"],["dc.contributor.author","Mamlouk, Soulafa"],["dc.contributor.author","Singh, Rashim Pal"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Muschter, Antje"],["dc.contributor.author","Olbrich, Susanne"],["dc.contributor.author","Breier, Georg"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Huttner, Wieland"],["dc.contributor.author","Weidemann, Alexander"],["dc.contributor.author","Wielockx, Ben"],["dc.date.accessioned","2018-11-07T09:20:59Z"],["dc.date.available","2018-11-07T09:20:59Z"],["dc.date.issued","2013"],["dc.description.abstract","Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of beta(3)-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1 alpha-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor beta signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds."],["dc.identifier.doi","10.1128/MCB.00609-13"],["dc.identifier.isi","000322817600004"],["dc.identifier.pmid","23798557"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29006"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0270-7306"],["dc.title","Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","34"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Veterinary research"],["dc.bibliographiccitation.lastpage","34"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Riekenberg, Sabine"],["dc.contributor.author","Jung, Günther"],["dc.contributor.author","Wiesmüller, Karl-Heinz"],["dc.contributor.author","Jungi, Thomas W."],["dc.contributor.author","Ulmer, Artur J."],["dc.date.accessioned","2019-07-09T11:53:04Z"],["dc.date.available","2019-07-09T11:53:04Z"],["dc.date.issued","2010"],["dc.description.abstract","Toll-like receptors (TLR) are highly conserved pattern recognition receptors of the innate immune system. Toll-like receptor 2 (TLR2) recognizes bacterial lipopeptides in a heterodimeric complex with TLR6 or TLR1, thereby discriminating between di- or triacylated lipopeptides, respectively. Previously, we found that HEK293 cells transfected with bovine TLR2 (boTLR2) were able to respond to diacylated lipopeptides but did not recognize triacylated lipopeptides, even after cotransfection with the so far published sequence of boTLR1. In this study we now could show that primary bovine cells were in general able to detect triacylated lipopetides. A closer investigation of the boTLR1 gene locus revealed an additional ATG 195 base pairs upstream from the published start codon. Its transcription would result in an N-terminus with high identity to human and murine TLR1 (huTLR1, muTLR1). Cloning and cotransfection of this longer boTLR1 with boTLR2 now resulted in the recognition of triacylated lipopeptides by HEK293 cells, thereby resembling the ex vivo observation. Analysis of the structure-activity relationship showed that the ester-bound acid chains of these lipopeptides need to consist of at least 12 carbon atoms to activate the bovine heterodimer showing similarity to the recognition by huTLR2/huTLR1. In contrast, HEK293 cell cotransfected with muTLR2 and muTLR1 could already be activated by lipopeptides with shorter fatty acids of only 6 carbon atoms. Thus, our data indicate that the additional N-terminal nucleotides belong to the full length and functionally active boTLR1 (boTLR1-fl) which participates in a species-specific recognition of bacterial lipopeptides."],["dc.identifier.doi","10.1051/vetres/2010006"],["dc.identifier.fs","576969"],["dc.identifier.pmid","20167196"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60334"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0928-4249"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Cattle"],["dc.subject.mesh","Cell Line"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Lipopeptides"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Toll-Like Receptor 1"],["dc.subject.mesh","Toll-Like Receptor 2"],["dc.title","Identification of full length bovine TLR1 and functional characterization of lipopeptide recognition by bovine TLR2/1 heterodimer."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]