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Buttler, Kerstin
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Buttler, Kerstin
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Buttler, Kerstin
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Buttler, K.
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2016-01-09Journal Article [["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Histochemistry and cell biology"],["dc.bibliographiccitation.lastpage","8"],["dc.contributor.author","Buttler, K."],["dc.contributor.author","Lohrberg, M."],["dc.contributor.author","Gross, G."],["dc.contributor.author","Weich, H. A."],["dc.contributor.author","Wilting, J."],["dc.date.accessioned","2019-07-09T11:42:09Z"],["dc.date.available","2019-07-09T11:42:09Z"],["dc.date.issued","2016-01-09"],["dc.description.abstract","The embryonic origin of lymphatic endothelial cells (LECs) has been a matter of controversy since more than a century. However, recent studies in mice have supported the concept that embryonic lymphangiogenesis is a complex process consisting of growth of lymphatics from specific venous segments as well as the integration of lymphangioblasts into the lymphatic networks. Similarly, the mechanisms of adult lymphangiogenesis are poorly understood and have rarely been studied. We have recently shown that endothelial progenitor cells isolated from the lung of adult mice have the capacity to form both blood vessels and lymphatics when grafted with Matrigel plugs into the skin of syngeneic mice. Here, we followed up on these experiments and studied the behavior of host leukocytes during lymphangiogenesis in the Matrigel plugs. We observed a striking co-localization of CD45(+) leukocytes with the developing lymphatics. Numerous CD45(+) cells expressed the LEC marker podoplanin and were obviously integrated into the lining of lymphatic capillaries. This indicates that, similar to inflammation-induced lymphangiogenesis in man, circulating CD45(+) cells of adult mice are capable of initiating lymphangiogenesis and of adopting a lymphvasculogenic cellular differentiation program. The data are discussed in the context of embryonic and inflammation-induced lymphangiogenesis."],["dc.identifier.doi","10.1007/s00418-015-1399-y"],["dc.identifier.pmid","26748643"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12904"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58601"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-119X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Integration of CD45-positive leukocytes into newly forming lymphatics of adult mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2011Journal Article [["dc.bibliographiccitation.firstpage","163"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Angiogenesis"],["dc.bibliographiccitation.lastpage","172"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Hemmen, Katherina"],["dc.contributor.author","Reinl, Tobias"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","Behler, Friederike"],["dc.contributor.author","Dieken, Hauke"],["dc.contributor.author","Jaensch, Lothar"],["dc.contributor.author","Wilting, Joerg"],["dc.contributor.author","Weich, Herbert A."],["dc.date.accessioned","2018-11-07T08:56:20Z"],["dc.date.available","2018-11-07T08:56:20Z"],["dc.date.issued","2011"],["dc.description.abstract","Recently, we isolated and characterized resident endothelial progenitor cells from the lungs of adult mice. These cells have a high proliferation potential, are not transformed and can differentiate into blood- and lymph-vascular endothelial cells under in vitro and in vivo conditions. Here we studied the secretome of these cells by nanoflow liquid chromatographic mass spectrometry (LC-MS). For analysis, 3-day conditioned serum-free media were used. We found 133 proteins belonging to the categories of membrane-bound or secreted proteins. Thereby, several of the membrane-bound proteins also existed as released variants. Thirty-five proteins from this group are well known as endothelial cell- or angiogenesis-related proteins. The MS analysis of the secretome was supplemented and confirmed by fluorescence activated cell sorting analyses, ELISA measurements and immunocytological studies of selected proteins. The secretome data presented in this study provides a platform for the in-depth analysis of endothelial progenitor cells and characterizes potential cellular markers and signaling components in hem- and lymphangiogeneis."],["dc.identifier.doi","10.1007/s10456-011-9200-x"],["dc.identifier.isi","000291038200006"],["dc.identifier.pmid","21234671"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23121"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0969-6970"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","High-resolution mass spectrometric analysis of the secretome from mouse lung endothelial progenitor cells"],["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"]]Details DOI PMID PMC WOS2017Journal Article [["dc.bibliographiccitation.artnumber","42523"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Subashini, Chandramohan"],["dc.contributor.author","Dhanesh, Sivadasan Bindu"],["dc.contributor.author","Chen, Chih-Ming"],["dc.contributor.author","Riya, Paul Ann"],["dc.contributor.author","Meera, Vadakkath"],["dc.contributor.author","Divya, Thulasi Sheela"],["dc.contributor.author","Kuruvilla, Rejji"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","James, Jackson"],["dc.date.accessioned","2018-11-07T10:27:23Z"],["dc.date.available","2018-11-07T10:27:23Z"],["dc.date.issued","2017"],["dc.description.abstract","The role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a(-/-) and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors. Furthermore, we show that the overall reduction is due to decreased radial glial and granule neuron progenitor cell proliferation. At molecular level we provide evidence for non-canonical mode of action of Wnt5a and its regulation over genes associated with progenitor proliferation. Altogether our findings imply that Wnt5a signaling is a crucial regulator of cerebellar development and would aid in better understanding of cerebellar disease pathogenesis caused due to deregulation of Wnt signaling."],["dc.identifier.doi","10.1038/srep42523"],["dc.identifier.isi","000394221300001"],["dc.identifier.pmid","28205531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14389"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43226"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Wnt5a is a crucial regulator of neurogenesis during cerebellum development"],["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"]]Details DOI PMID PMC WOS2010Journal Article [["dc.bibliographiccitation.artnumber","50"],["dc.bibliographiccitation.journal","BMC Cell Biology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Schniedermann, Judith"],["dc.contributor.author","Rennecke, Moritz"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","Richter, Georg"],["dc.contributor.author","Staedtler, Anna-Maria"],["dc.contributor.author","Norgall, Susanne"],["dc.contributor.author","Badar, Muhammad"],["dc.contributor.author","Barleon, Bernhard"],["dc.contributor.author","May, Tobias"],["dc.contributor.author","Wilting, Joerg"],["dc.contributor.author","Weich, Herbert A."],["dc.date.accessioned","2018-11-07T08:41:30Z"],["dc.date.available","2018-11-07T08:41:30Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results: In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs) were isolated by selection of CD31(+) cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony). These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs) in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion: The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell."],["dc.identifier.doi","10.1186/1471-2121-11-50"],["dc.identifier.isi","000282731800001"],["dc.identifier.pmid","20594323"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5672"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19484"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2121"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels"],["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"]]Details DOI PMID PMC WOS2016Journal Article [["dc.bibliographiccitation.artnumber","e0164964"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hasselhof, Viktoria"],["dc.contributor.author","Sperling, Anastasia"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","Strobel, Philipp"],["dc.contributor.author","Becker, Juergen"],["dc.contributor.author","Aung, Thiha"],["dc.contributor.author","Felmerer, Gunther"],["dc.contributor.author","Wilting, Joerg"],["dc.date.accessioned","2018-11-07T10:06:56Z"],["dc.date.available","2018-11-07T10:06:56Z"],["dc.date.issued","2016"],["dc.description.abstract","Millions of patients suffer from lymphedema worldwide. Supporting the contractility of lymphatic collectors is an attractive target for pharmacological therapy of lymphedema. However, lymphatics have mostly been studied in animals, while the cellular and molecular characteristics of human lymphatic collectors are largely unknown. We studied epifascial lymphatic collectors of the thigh, which were isolated for autologous transplantations. Our immunohistological studies identify additional markers for LECs (vimentin, CCBE1). We show and confirm differences between initial and collecting lymphatics concerning the markers ESAM1, D2-40 and LYVE-1. Our transmission electron microscopic studies reveal two types of smooth muscle cells (SMCs) in the media of the collectors with dark and light cytoplasm. We observed vasa vasorum in the media of the largest collectors, as well as interstitial Cajal-like cells, which are highly ramified cells with long processes, caveolae, and lacking a basal lamina. They are in close contact with SMCs, which possess multiple caveolae at the contact sites. Immunohistologically we identified such cells with antibodies against vimentin and PDGFR alpha, but not CD34 and cKIT. With Next Generation Sequencing we searched for highly expressed genes in the media of lymphatic collectors, and found therapeutic targets, suitable for acceleration of lymphatic contractility, such as neuropeptide Y receptors 1, and 5; tachykinin receptors 1, and 2; purinergic receptors P2RX1, and 6, P2RY12, 13, and 14; 5-hydroxytryptamine receptors HTR2B, and 3C; and adrenoceptors alpha(2A),(B),(C). Our studies represent the first comprehensive characterization of human epifascial lymphatic collectors, as a prerequisite for diagnosis and therapy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0164964"],["dc.identifier.isi","000386204500086"],["dc.identifier.pmid","27764183"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39190"],["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","Morphological and Molecular Characterization of Human Dermal Lymphatic Collectors"],["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"]]Details DOI PMID PMC WOS2019Journal Article [["dc.bibliographiccitation.artnumber","4739"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Lutze, Grit"],["dc.contributor.author","Haarmann, Anna"],["dc.contributor.author","Demanou Toukam, Jules A"],["dc.contributor.author","Buttler, Kerstin"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Becker, Jürgen"],["dc.date.accessioned","2019-07-09T11:50:33Z"],["dc.date.available","2019-07-09T11:50:33Z"],["dc.date.issued","2019"],["dc.description.abstract","Development of lymphatics takes place during embryogenesis, wound healing, inflammation, and cancer. We previously showed that Wnt5a is an essential regulator of lymphatic development in the dermis of mice, however, the mechanisms of action remained unclear. Here, whole-mount immunostaining shows that embryonic day (ED) 18.5 Wnt5a-null mice possess non-functional, cyst-like and often blood-filled lymphatics, in contrast to slender, interconnected lymphatic networks of Wnt5a+/- and wild-type (wt) mice. We then compared lymphatic endothelial cell (LEC) proliferation during ED 12.5, 14.5, 16.5 and 18.5 between Wnt5a-/-, Wnt5a+/- and wt-mice. We did not observe any differences, clearly showing that Wnt5a acts independently of proliferation. Transmission electron microscopy revealed multiple defects of LECs in Wnt5a-null mice, such as malformed inter-endothelial junctions, ruffled cell membrane, intra-luminal bulging of nuclei and cytoplasmic processes. Application of WNT5A protein to ex vivo cultures of dorsal thoracic dermis from ED 15.5 Wnt5a-null mice induced flow-independent development of slender, elongated lymphatic networks after 2 days, in contrast to controls showing an immature lymphatic plexus. Reversely, the application of the WNT-secretion inhibitor LGK974 on ED 15.5 wt-mouse dermis significantly prevented lymphatic network elongation. Correspondingly, tube formation assays with human dermal LECs in vitro revealed increased tube length after WNT5A application. To study the intracellular signaling of WNT5A we used LEC scratch assays. Thereby, inhibition of autocrine WNTs suppressed horizontal migration, whereas application of WNT5A to inhibitor-treated LECs promoted migration. Inhibition of the RHO-GTPase RAC, or the c-Jun N-terminal kinase JNK significantly reduced migration, whereas inhibitors of the protein kinase ROCK did not. WNT5A induced transient phosphorylation of JNK in LECs, which could be inhibited by RAC- and JNK-inhibitors. Our data show that WNT5A induces formation of elongated lymphatic networks through proliferation-independent WNT-signaling via RAC and JNK. Non-canonical WNT-signaling is a major mechanism of extension lymphangiogenesis, and also controls differentiation of lymphatics."],["dc.identifier.doi","10.1038/s41598-019-41299-7"],["dc.identifier.pmid","30894622"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15960"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59793"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Non-canonical WNT-signaling controls differentiation of lymphatics and extension lymphangiogenesis via RAC and JNK signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC