Lutz, Susanne

[["dc.bibliographiccitation.artnumber","276"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Hartmann, Svenja"],["dc.contributor.author","Ridley, Anne J."],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2018-11-07T09:48:49Z"],["dc.date.available","2018-11-07T09:48:49Z"],["dc.date.issued","2015"],["dc.description.abstract","Rho associated kinases ROCK1 and ROCK2 are serine/threonine kinases that are downstream targets of the small GTPases RhoA, RhoB, and RhoC. ROCKs are involved in diverse cellular activities including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, remodeling of the extracellular matrix and smooth muscle cell contraction. The role of ROCK1 and ROCK2 has long been considered to be similar; however, it is now clear that they do not always have the same functions. Moreover, depending on their subcellular localization, activation, and other environmental factors, ROCK signaling can have different effects on cellular function. With respect to the heart, findings in isoform-specific knockout mice argue for a role of ROCK1 and ROCK2 in the pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively. Increased ROCK activity could play a pivotal role in processes leading to cardiovascular diseases such as hypertension, pulmonary hypertension, angina pectoris, yasospastic angina, heart failure, and stroke, and thus ROCK activity is a potential new biomarker for heart disease. Pharmacological ROCK inhibition reduces the enhanced ROCK activity in patients, accompanied with a measurable improvement in medical condition. In this review, we focus on recent findings regarding ROCK signaling in the pathogenesis of cardiovascular disease, with a special focus on differences between ROCK1 and ROCK2 function."],["dc.identifier.doi","10.3389/fphar.2015.00276"],["dc.identifier.isi","000366126900001"],["dc.identifier.pmid","26635606"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35386"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/116"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation.eissn","1663-9812"],["dc.relation.issn","1663-9812"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","741"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Weber, Pamina"],["dc.contributor.author","Baltus, Doris"],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Drews, Oliver"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2021-06-01T09:42:32Z"],["dc.date.available","2021-06-01T09:42:32Z"],["dc.date.issued","2021"],["dc.description.abstract","The Rho guanine nucleotide exchange factor RhoGEF17 was described to reside in adherens junctions (AJ) in endothelial cells (EC) and to play a critical role in the regulation of cell adhesion and barrier function. The purpose of this study was to analyze signal cascades and processes occurring subsequent to AJ disruption induced by RhoGEF17 knockdown. Primary human and immortalized rat EC were used to demonstrate that an adenoviral-mediated knockdown of RhoGEF17 resulted in cell rounding and an impairment in spheroid formation due to an enhanced proteasomal degradation of AJ components. In contrast, β-catenin degradation was impaired, which resulted in an induction of the β-catenin-target genes cyclin D1 and survivin. RhoGEF17 depletion additionally inhibited cell adhesion and sheet migration. The RhoGEF17 knockdown prevented the cells with impeded cell–cell and cell–matrix contacts from apoptosis, which was in line with a reduction in pro-caspase 3 expression and an increase in Akt phosphorylation. Nevertheless, the cells were not able to proliferate as a cell cycle block occurred. In summary, we demonstrate that a loss of RhoGEF17 disturbs cell–cell and cell–substrate interaction in EC. Moreover, it prevents the EC from cell death and blocks cell proliferation. Non-canonical β-catenin signaling and Akt activation could be identified as a potential mechanism."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells10040741"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85279"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/391"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation.eissn","2073-4409"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","RhoGEF17—An Essential Regulator of Endothelial Cell Death and Growth"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0137519"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Hartmann, Svenja"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Muegge, Felicitas"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2017-09-07T11:43:28Z"],["dc.date.available","2017-09-07T11:43:28Z"],["dc.date.issued","2015"],["dc.description.abstract","Introduction RhoA has been shown to be beneficial in cardiac disease models when overexpressed in cardiomyocytes, whereas its role in cardiac fibroblasts (CF) is still poorly understood. During cardiac remodeling CF undergo a transition towards a myofibroblast phenotype thereby showing an increased proliferation and migration rate. Both processes involve the remodeling of the cytoskeleton. Since RhoA is known to be a major regulator of the cytoskeleton, we analyzed its role in CF and its effect on myofibroblast characteristics in 2 D and 3D models. Results Downregulation of RhoA was shown to strongly affect the actin cytoskeleton. It decreased the myofibroblast marker alpha-sm-actin, but increased certain fibrosis-associated factors like TGF-beta and collagens. Also, the detailed analysis of CTGF expression demonstrated that the outcome of RhoA signaling strongly depends on the involved stimulus. Furthermore, we show that proliferation of myofibroblasts rely on RhoA and tubulin acetylation. In assays accessing three different types of migration, we demonstrate that RhoA/ROCK/Dia1 are important for 2D migration and the repression of RhoA and Dia1 signaling accelerates 3D migration. Finally, we show that a downregulation of RhoA in CF impacts the viscoelastic and contractile properties of engineered tissues. Conclusion RhoA positively and negatively influences myofibroblast characteristics by differential signaling cascades and depending on environmental conditions. These include gene expression, migration and proliferation. Reduction of RhoA leads to an increased viscoelasticity and a decrease in contractile force in engineered cardiac tissue."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1371/journal.pone.0137519"],["dc.identifier.gro","3141809"],["dc.identifier.isi","000362511000003"],["dc.identifier.pmid","26448568"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1312"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/118"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | C06: Mechanismen und Regulation der koronaren Gefäßneubildung"],["dc.relation.issn","1932-6203"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RhoA Ambivalently Controls Prominent Myofibroblast Characteritics by Involving Distinct Signaling Routes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","461"],["dc.bibliographiccitation.issue","4-5"],["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.lastpage","472"],["dc.bibliographiccitation.volume","384"],["dc.contributor.author","Hippe, Hans-Joerg"],["dc.contributor.author","Wolf, Nadine M."],["dc.contributor.author","Abu-Taha, Issam H."],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Le Lay, Soazig"],["dc.contributor.author","Just, Steffen"],["dc.contributor.author","Rottbauer, Wolfgang"],["dc.contributor.author","Katus, Hugo A."],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2018-11-07T08:51:02Z"],["dc.date.available","2018-11-07T08:51:02Z"],["dc.date.issued","2011"],["dc.description.abstract","Caveolae are flask-shaped invaginations in the plasma membrane that serve to compartmentalize and organize signal transduction processes, including signals mediated by G protein-coupled receptors and heterotrimeric G proteins. Herein we report evidence for a close association of the nucleoside diphosphate kinase B (NDPK B) and caveolin proteins which is required for G protein scaffolding and caveolae formation. A concomitant loss of the proteins NDPK B, caveolin isoforms 1 (Cav1) and 3, and heterotrimeric G proteins occurred when one of these proteins was specifically depleted in zebrafish embryos. Co-immunoprecipitation of Cav1 with the G protein G beta-subunit and NDPK B from zebrafish lysates corroborated the direct association of these proteins. Similarly, in embryonic fibroblasts from the respective knockout (KO) mice, the membrane content of the Cav1, G beta, and NDPK B was found to be mutually dependent on one another. A redistribution of Cav1 and G beta from the caveolae containing fractions of lower density to other membrane compartments with higher density could be detected by means of density gradient fractionation of membranes derived from NDPK A/B KO mouse embryonic fibroblasts (MEFs) and after shRNA-mediated NDPK B knockdown in H10 cardiomyocytes. This redistribution could be visualized by confocal microscopy analysis showing a decrease in the plasma membrane bound Cav1 in NDPK A/B KO cells and vice versa and a decrease in the plasma membrane pool of NDPK B in Cav1 KO cells. Consequently, ultrastructural analysis revealed a reduction of surface caveolae in the NDPK A/B KO cells. To prove that the disturbed subcellular localization of Cav1 in NDPK A/B KO MEFs as well as NDPK B in Cav1 KO MEFs is a result of the loss of NDPK B and Cav1, respectively, we performed rescue experiments. The adenoviral re-expression of NDPK B in NDPK A/B KO MEFs rescued the protein content and the plasma membrane localization of Cav1. The expression of an EGFP-Cav1 fusion protein in Cav1-KO cells induced a restoration of NDPK B expression levels and its appearance at the plasma membrane. We conclude from these findings that NDPK B, heterotrimeric G proteins, and caveolins are mutually dependent on each other for stabile localization and caveolae formation at the plasma membrane. The data point to a disturbed transport of caveolin/G protein/NDPK B complexes from intracellular membrane compartments if one of the components is missing."],["dc.identifier.doi","10.1007/s00210-011-0618-x"],["dc.identifier.isi","000296639000014"],["dc.identifier.pmid","21409430"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21835"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0028-1298"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nucleoside diphosphate kinase B is required for the formation of heterotrimeric G protein containing caveolae"],["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","4865"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","4876"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Lorincz, Akos"],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Thomas, Martin A."],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2018-11-07T08:36:13Z"],["dc.date.available","2018-11-07T08:36:13Z"],["dc.date.issued","2010"],["dc.description.abstract","The purpose of our study was to investigate the role of endogenous p63RhoGEF in G(q/11)-dependent RhoA activation and signaling in rat aortic smooth muscle cells (RASMCs). Therefore, we studied the expression and subcellular localization in freshly isolated RASMCs and performed loss of function experiments to analyze its contribution to RhoGTPase activation and functional responses such as proliferation and contraction. By this, we could show that p63RhoGEF is endogenously expressed in RASMCs and acts there as the dominant mediator of the fast angiotensin II (ANG II)-dependent but not of the sphingosine-1-phosphate (S1P)-dependent RhoA activation. p63RhoGEF is not an activator of the concomitant Rac1 activation and functions independently of caveolae. The knockdown of endogenous p63RhoGEF significantly reduced the mitogenic response of ANG II, abolished ANG II-induced stress fiber formation and cell elongation in 2-D culture, and impaired the ANG II-driven contraction in a collagen-based 3-D model. In conclusion, our data provide for the first time evidence that p63RhoGEF is an important mediator of ANG II-dependent RhoA activation in RASMCs and therewith a leading actor in the subsequently triggered cellular processes, such as proliferation and contraction.-Wuertz, C. M., Lorincz, A., Vettel, C., Thomas, M. A., Wieland, T., Lutz, S. p63RhoGEF-a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells. FASEB J. 24, 4865-4876 (2010). www.fasebj.org"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [Lu1486/1-1, SFB TR 23 TP B6]"],["dc.identifier.doi","10.1096/fj.10-155499"],["dc.identifier.isi","000284824400026"],["dc.identifier.pmid","20739613"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6271"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18258"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","p63RhoGEF-a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","989"],["dc.bibliographiccitation.journal","International Journal of Nanomedicine"],["dc.bibliographiccitation.lastpage","1000"],["dc.bibliographiccitation.volume","Volume 16"],["dc.contributor.author","Kittana, Naim"],["dc.contributor.author","Assali, Mohyeddin"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Liaw, Norman"],["dc.contributor.author","Santos, Gabriela Leao"],["dc.contributor.author","Rehman, Abdul"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2021-04-14T08:29:53Z"],["dc.date.available","2021-04-14T08:29:53Z"],["dc.date.issued","2021"],["dc.description.abstract","Background: Under certain conditions, the physiological repair of connective tissues might fail to restore the original structure and function. Optimized engineered connective tissues (ECTs) with biophysical properties adapted to the target tissue could be used as a substitution therapy. This study aimed to investigate the effect of ECT enforcement by a complex of multiwall carbon nanotubes with chitosan (C-MWCNT) to meet in vivo demands.\r\nMaterials and Methods: ECTs were constructed from human foreskin fibroblasts (HFF-1) in collagen type I and enriched with the three different percentages 0.025, 0.05 and 0.1% of C-MWCNT. Characterization of the physical properties was performed by biomechanical studies using unidirectional strain.\r\nResults: Supplementation with 0.025% C-MWCNT moderately increased the tissue stiffness, reflected by Young’s modulus, compared to tissues without C-MWCNT. Supplementation of ECTs with 0.1% C-MWCNT reduced tissue contraction and increased the elasticity and the extensibility, reflected by the yield point and ultimate strain, respectively. Consequently, the ECTs with 0.1% C-MWCNT showed a higher resilience and toughness as control tissues. Fluorescence tissue imaging demonstrated the longitudinal alignment of all cells independent of the condition.\r\nConclusion: Supplementation with C-MWCNT can enhance the biophysical properties of ECTs, which could be advantageous for applications in connective tissue repair."],["dc.identifier.doi","10.2147/IJN.S289107"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83018"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/387"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1178-2013"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC 3.0"],["dc.title","Modulating the Biomechanical Properties of Engineered Connective Tissues by Chitosan-Coated Multiwall Carbon Nanotubes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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","13"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","28"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Santos, Gabriela Leão"],["dc.contributor.author","Hartmann, Svenja"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Ridley, Anne"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2020-12-10T15:21:48Z"],["dc.date.available","2020-12-10T15:21:48Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.yjmcc.2019.06.015"],["dc.identifier.pmid","31233754"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16472"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73169"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/304"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Inhibition of Rho-associated kinases suppresses cardiac myofibroblast function in engineered connective and heart muscle tissues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","8"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Levay, Magdolna K."],["dc.contributor.author","Krobert, Kurt A."],["dc.contributor.author","Vogt, Andreas"],["dc.contributor.author","Ahmad, Atif"],["dc.contributor.author","Jungmann, Andreas"],["dc.contributor.author","Neuber, Christiane"],["dc.contributor.author","Pasch, Sebastian"],["dc.contributor.author","Hansen, Arne"],["dc.contributor.author","Müller, Oliver J."],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wieland, Thomas"],["dc.date.accessioned","2022-04-01T10:01:10Z"],["dc.date.available","2022-04-01T10:01:10Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract The role and outcome of the muscarinic M 2 acetylcholine receptor (M 2 R) signaling in healthy and diseased cardiomyocytes is still a matter of debate. Here, we report that the long isoform of the regulator of G protein signaling 3 (RGS3L) functions as a switch in the muscarinic signaling, most likely of the M 2 R, in primary cardiomyocytes. High levels of RGS3L, as found in heart failure, redirect the G i -mediated Rac1 activation into a G i -mediated RhoA/ROCK activation. Functionally, this switch resulted in a reduced production of reactive oxygen species (− 50%) in cardiomyocytes and an inotropic response (+ 18%) in transduced engineered heart tissues. Importantly, we could show that an adeno-associated virus 9-mediated overexpression of RGS3L in rats in vivo, increased the contractility of ventricular strips by maximally about twofold. Mechanistically, we demonstrate that this switch is mediated by a complex formation of RGS3L with the GTPase-activating protein p190RhoGAP, which balances the activity of RhoA and Rac1 by altering its substrate preference in cardiomyocytes. Enhancement of this complex formation could open new possibilities in the regulation of the contractility of the diseased heart."],["dc.identifier.doi","10.1007/s00395-022-00915-w"],["dc.identifier.pii","915"],["dc.identifier.pmid","35230541"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105615"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/440"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C02: RhoGTPasen und ihre Bedeutung für die Last-abhängige Myokardfibrose"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","RGS3L allows for an M2 muscarinic receptor-mediated RhoA-dependent inotropy in cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]