Regulation of endothelin-1 gene expression by cell shape and the microfilament network in vascular endothelium

1997 ◽  
Vol 273 (5) ◽  
pp. C1764-C1774 ◽  
Author(s):  
Adel Moussa Malek ◽  
Ike W. Lee ◽  
Seth L. Alper ◽  
Seigo Izumo
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Cell Contact ◽  
Bovine Aortic Endothelial Cell ◽  
Mrna Levels ◽  
Endothelin 1 ◽  
Cell Shape Change ◽  
Dose Dependent

Endothelial synthesis and release of endothelin-1 (ET-1) are exquisitely regulated by external shear and strain. We tested the hypothesis that manipulation of endothelial cell shape can regulate ET-1 gene expression. Treatment of bovine aortic endothelial cell (BAEC) monolayers with cytochalasin D disrupted F-actin and induced cell retraction and rounding, in parallel with time- and dose-dependent specific decreases in ET-1 mRNA levels. Treatments with forskolin, phorbol 12-myristate 13-acetate, staurosporine, and genistein also induced cell shape change and decreased F-actin staining and ET-1 mRNA levels. BAEC plated onto nonadhesive petri dishes coated with decreasing concentrations of synthetic RGD polymer showed RGD dose-dependent decreases in cell spreading and in F-actin microfilament elaboration. These changes were specifically accompanied by decreases in ET-1 peptide secretion (60%) and, via posttranscriptional mechanisms, ET-1 mRNA (94%) and were not due to decreased cell-cell contact. We conclude that the shape and microfilament network of endothelial cells are potent posttranscriptional regulators of ET-1 gene expression.

scholarly journals Gαq-TRPC6-mediated Ca2+Entry Induces RhoA Activation and Resultant Endothelial Cell Shape Change in Response to Thrombin

2006 ◽  
Vol 282 (11) ◽  
pp. 7833-7843 ◽  
Author(s):  
Itender Singh ◽  
Nebojsa Knezevic ◽  
Gias U. Ahmmed ◽  
Vidisha Kini ◽  
Asrar B. Malik ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Rhoa Activation ◽  
Cell Shape Change

scholarly journals Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile

2021 ◽  
Vol 22 (4) ◽  
pp. 2219
Author(s):  
Ning Wang ◽  
Haiying Zhang ◽  
Xiulin Cui ◽  
Chao Ma ◽  
Linghui Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Actin Cytoskeleton ◽  
Cell Shape ◽  
Shape Change ◽  
Hdac Inhibitors ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Transcriptional Profile ◽  
Cell Shape Change ◽  
Related Transcription Factor

Runt-related transcription factor-3 (Runx3) is a tumor suppressor, and its contribution to melanoma progression remains unclear. We previously demonstrated that Runx3 re-expression in B16-F10 melanoma cells changed their shape and attenuated their migration. In this study, we found that Runx3 re-expression in B16-F10 cells also suppressed their pulmonary metastasis. We performed microarray analysis and uncovered an altered transcriptional profile underlying the cell shape change and the suppression of migration and metastasis. This altered transcriptional profile was rich in Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotations relevant to adhesion and the actin cytoskeleton and included differentially expressed genes for some major extracellular matrix (ECM) proteins as well as genes that were inversely associated with the increase in the metastatic potential of B16-F10 cells compared to B16-F0 melanoma cells. Further, we found that this altered transcriptional profile could have prognostic value, as evidenced by myelin and lymphocyte protein (MAL) and vilin-like (VILL). Finally, Mal gene expression was correlated with metastatic potential among the cells and was targeted by histone deacetylase (HDAC) inhibitors in B16-F10 cells, and the knockdown of Mal gene expression in B16-F0 cells changed their shape and enhanced the migratory and invasive traits of their metastasis. Our study suggests that self-entrapping of metastatic Runx3-negative melanoma cells via adhesion and the actin cytoskeleton could be a powerful therapeutic strategy.

scholarly journals Establishment of morphological atlas of Caenorhabditis elegans embryo with cellular resolution using deep-learning-based 4D segmentation

2019 ◽  
Author(s):  
Jianfeng Cao ◽  
Guoye Guan ◽  
Ming-Kin Wong ◽  
Lu-Yan Chan ◽  
Chao Tang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Biology ◽  
Cell Shape ◽  
Shape Change ◽  
Shape Reconstruction ◽  
Cell Contact ◽  
Spatiotemporal Resolution ◽  
C Elegans ◽  
Cell Shape Change ◽  
Cell Cell

Cell lineage consists of cell division timing, cell migration and cell fate, which are highly reproducible during the development of some nematode species, including C. elegans. Due to the lack of high spatiotemporal resolution of imaging technique and reliable shape-reconstruction algorithm, cell morphology have not been systematically characterized in depth over development for any metazoan. This significantly inhibits the study of space-related problems in developmental biology, including cell segregation, cell-cell contact and cell shape change over development. Here we develop an automated pipeline, CShaper, to help address these issues. By quantifying morphological parameters of densely packed cells in developing C. elegans emrbyo through segmentation of fluorescene-labelled membrance, we generate a time-lapse framework of cellular shape and migration for C. elegans embryos from 4-to 350-cell stage, including a full migration trajectory, morphological dynamics of 226 cells and 877 reproducible cell-cell contacts. In combination with automated cell tracing, cell-fate associated cell shape change becomes within reach. Our work provides a quantitative resource for C. elegans early development, which is expected to facilitate the research such as signaling transduction and cell biology of division.

scholarly journals Mechanism of endothelial cell shape change in oxidant injury

1989 ◽  
Vol 46 (4) ◽  
pp. 339-349 ◽  
Author(s):  
Daniel B. Hinshaw ◽  
Jeanne M. Burger ◽  
Barbara C. Armstrong ◽  
Paul A. Hyslop
Keyword(s):  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Oxidant Injury ◽  
Cell Shape Change

Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1

1998 ◽  
Vol 275 (3) ◽  
pp. L574-L582 ◽  
Author(s):  
Timothy M. Moore ◽  
George H. Brough ◽  
Paul Babal ◽  
John J. Kelly ◽  
Ming Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Shape ◽  
Transient Receptor Potential ◽  
Shape Change ◽  
Filamentous Actin ◽  
Cell Shape Change ◽  
Pulmonary Endothelial Cells ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells

Activation of Ca2+ entry is known to produce endothelial cell shape change, leading to increased permeability, leukocyte migration, and initiation of angiogenesis in conduit-vessel endothelial cells. The mode of Ca2+ entry regulating cell shape is unknown. We hypothesized that activation of store-operated Ca2+ channels (SOCs) is sufficient to promote cell shape change necessary for these processes. SOC activation in rat pulmonary arterial endothelial cells increased free cytosolic Ca2+ that was dependent on a membrane current having a net inward component of 5.45 ± 0.90 pA/pF at −80 mV. Changes in endothelial cell shape accompanied SOC activation and were dependent on Ca2+ entry-induced reconfiguration of peripheral (cortical) filamentous actin (F-actin). Because the identity of pulmonary endothelial SOCs is unknown, but mammalian homologues of the Drosophila melanogaster transient receptor potential ( trp) gene have been proposed to form Ca2+ entry channels in nonexcitable cells, we performed RT-PCR using Trp oligonucleotide primers in both rat and human pulmonary arterial endothelial cells. Both cell types were found to express Trp1, but neither expressed Trp3 nor Trp6. Our study indicates that 1) Ca2+ entry in pulmonary endothelial cells through SOCs produces cell shape change that is dependent on site-specific rearrangement of the microfilamentous cytoskeleton and 2) Trp1 may be a component of pulmonary endothelial SOCs.

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