Extracorporeal shockwave treatment was shown to improve orthopaedic diseases, wound healing and to stimulate lymphangiogenesis in vivo. The aim of this study was to investigate in vitro shockwave treatment (IVSWT) effects on lymphatic endothelial cell (LEC) behavior and lymphangiogenesis. We analyzed migration, proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo.
Molecular and cellular effects of in vitro shockwave treatment on lymphatic endothelial cells.
Specimen part
View SamplesGRBATKO_BAT_COLDEXPOSURE
The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis.
Specimen part
View SamplesThe RNA-binding protein RC3H1 (also known as ROQUIN) promotes TNFalpha mRNA decay via a 3''UTR constitutive decay element (CDE). Here, we applied PAR-CLIP to human RC3H1 to identify about 3800 mRNA targets with more than 16000 binding sites. A large number of sites are distinct from the consensus CDE and revealed a structure-sequence motif with U-rich sequences embedded in hairpins. RC3H1 binds preferentially short-lived and DNA damage induced mRNAs, indicating a role of this RNA-binding protein in the posttranscriptional regulation of the DNA damage response. Intriguingly, RC3H1 affects expression of NF-kB pathway regulators such as IkBalpha and A20. RC3H1 uses roquin and Zn-finger domains to contact a binding site in the A20 3''UTR, demonstrating a not yet recognized mode of RC3H1 binding. Knockdown of RC3H1 resulted in increased A20 protein expression, thereby interfering with IkB kinase and NF-kB activities, demonstrating that RC3H1 can modulate the activity of the IKK/NF-kB pathway. Overall design: We measured global mRNA decay rates in mock and RC3H1/RC3H2-depleted HEK293 cells. Transcription was blocked by Actinomycin D zero, one or two hours before harvesting. Total RNA was isolated in two biological replicates and subjected to polyA selection followed by high-throughput sequencing.
RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-κB pathway.
No sample metadata fields
View SamplesMalignant Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. We depleted subunit combinations corresponding to either canonical (p50/RelA) or non-canonical (p52/RelB) dimers in the HL cell line L-1236 and performed Affymetrix microarray analysis. Knockdown of p52/RelB affected the expression of a significantly higher number of genes than the knockdown of p50/RelA. The two sets of target genes presented a partial overlap, however they also revealed specific genes that are involved in distinct aspects of tumor biology.
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Cell line, Treatment
View SamplesMalignant cells of Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-B signaling cascades. Knockdown of a subunit combination corresponding to the non-canonical NF-B dimer (p52/RelB) in the HL cell line L-1236 caused up-regulation of a set of genes that are associated with hematopoietic and lymphoid organ development. As p52 can form homodimeric complexes, which can repress transcription either alone or in association with transcriptional repressors such as HDAC1, we knocked down p52 alone to analyze its role in gene repression in HL cells. We found that the single knockdown of p52 is indeed sufficient to up-regulate an interesting set of genes that may play a role in B-cell and/or HL development.
A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.
Cell line, Treatment
View SamplesTreatment induced senescence (TIS) is a terminal cell cycle arrest program, increasingly recognized as a tumor suppressor mechanism complementing apoptosis in response to standard chemotherapy regimens. In particular cells with blocked apoptotic pathways rely on senescence as the only remaining failsafe mechanism to keep the neoplastic growth in check. However, little is known about biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment.
Opposing roles of NF-κB in anti-cancer treatment outcome unveiled by cross-species investigations.
No sample metadata fields
View SamplesRat kidney in normo- and hypotensive animals.
A physiogenomic approach to study the regulation of blood pressure.
No sample metadata fields
View SamplesAnalysis of transcriptional changes upon persistent heat stress with emphasis on epigenetically regulated genes
Epigenetic regulation of repetitive elements is attenuated by prolonged heat stress in Arabidopsis.
Specimen part
View SamplesWe investigated the expression profiles in the CD4+, CD8, and CD14+ peripheral blood cells (PBLs) of the stage IV melanoma patients and the healthy donors. Overall design: Examination of long noncoding RNA in the CD4+, CD8, and CD14+ peripheral blood cells (PBLs) of the stage IV melanoma patients and the healthy donors.
Integrative Genome-Wide Analysis of Long Noncoding RNAs in Diverse Immune Cell Types of Melanoma Patients.
Specimen part, Subject
View SamplesGenome-wide gene expression analysis of Reh cells following transfection with constitutively active IRF5-4D, constitutively active IKK(EE), or both in combination.
Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.
Cell line
View Samples