scholarly journals Laminin-511 and α6 Integrins Regulate the Expression of CXCR4 to Promote Endothelial Morphogenesis

2019 ◽  
Author(s):  
Hao Xu ◽  
Kevin Pumiglia ◽  
Susan E. LaFlamme
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Endothelial Cells ◽  
Gene Expression Analysis ◽  
Tube Formation ◽  
Integrin Expression ◽  
Dependent Inhibition ◽  
Summary Statement ◽  
Vessel Stability ◽  
Laminin 411

AbstractDuring angiogenesis, endothelial cells engage components of the extracellular matrix through integrin-mediated adhesion. Endothelial expression of laminin-411 and laminin-511 are known to promote vessel stability. However, little is known about the contribution of these laminins to endothelial morphogenesis. We used two organotypic cell culture angiogenesis assays in conjunction with RNAi approaches to demonstrate that depletion of either the α4 chain of laminin-411 or the α5 chain of laminin-511 from endothelial cells inhibits sprouting and tube formation. Depletion of α6 integrins resulted in similar phenotypes. Gene expression analysis indicated that loss of either laminin-511 or α6 integrins inhibited the expression of CXCR4, a gene previously associated with angiogenic endothelial cells. Pharmacological or RNAi-dependent inhibition of CXCR4 suppressed endothelial sprouting and morphogenesis. Importantly, expression of recombinant CXCR4 rescued endothelial morphogenesis when the α6 integrin expression was inhibited. Additionally, the depletion of α6 integrins from established tubes resulted in the loss of tube integrity and laminin-511. Taken together, our results indicate that α6 integrins and laminin-511 can promote endothelial morphogenesis by regulating the expression of CXCR4 and suggest that the α6-dependent deposition of laminin-511 protects the integrity of established endothelial tubes.Summary statementEndothelial-secreted laminin-511 and α6 integrins promote endothelial morphogenesis by regulating the expression of the chemokine receptor, CXCR4. The depletion of α6 integrins from established tubes results in the loss of tube integrity and laminin-511.

scholarly journals Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 621
Author(s):  
Maria Grazia Muoio ◽  
Marianna Talia ◽  
Rosamaria Lappano ◽  
Andrew H. Sims ◽  
Veronica Vella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Bioinformatic Analysis ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
Diabetic Patients ◽  
Obesity And Diabetes ◽  
Er Positive

Background: Breast cancer (BC) mortality is increased among obese and diabetic patients. Both obesity and diabetes are associated with dysregulation of both the IGF-1R and the RAGE (Receptor for Advanced Glycation End Products) pathways, which contribute to complications of these disorders. The alarmin S100A7, signaling through the receptor RAGE, prompts angiogenesis, inflammation, and BC progression. Methods: We performed bioinformatic analysis of BC gene expression datasets from published studies. We then used Estrogen Receptor (ER)-positive BC cells, CRISPR-mediated IGF-1R KO BC cells, and isogenic S100A7-transduced BC cells to investigate the role of IGF-1/IGF-1R in the regulation of S100A7 expression and tumor angiogenesis. To this aim, we also used gene silencing and pharmacological inhibitors, and we performed gene expression and promoter studies, western blotting analysis, ChIP and ELISA assays, endothelial cell proliferation and tube formation assay. Results: S100A7 expression correlates with worse prognostic outcomes in human BCs. In BC cells, the IGF-1/IGF-1R signaling engages STAT3 activation and its recruitment to the S100A7 promoter toward S100A7 increase. In human vascular endothelial cells, S100A7 activates RAGE signaling and prompts angiogenic effects. Conclusions: In ER-positive BCs the IGF-1 dependent activation of the S100A7/RAGE signaling in adjacent endothelial cells may serve as a previously unidentified angiocrine effector. Targeting S100A7 may pave the way for a better control of BC, particularly in conditions of unopposed activation of the IGF-1/IGF-1R axis.

scholarly journals The integrin coactivator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4978-4987 ◽  
Author(s):  
Elzbieta Pluskota ◽  
James J. Dowling ◽  
Natalie Gordon ◽  
Jeffrey A. Golden ◽  
Dorota Szpak ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Critical Role ◽  
Integrin Αvβ3 ◽  
Tube Formation ◽  
Basement Membranes ◽  
Cytoskeletal Protein ◽  
Integrin Expression ◽  
Partial Reduction ◽  
Wild Type ◽  
Developmental Defects

Abstract Kindlin-2, a widely distributed cytoskeletal protein, has been implicated in integrin activation, and its absence is embryonically lethal in mice and causes severe developmental defects in zebrafish. Knockdown of kindlin-2 levels in endothelial cells resulted in defective adhesive and migratory responses, suggesting that angiogenesis might be aberrant even with partial reduction of kindlin-2. This hypothesis has now been tested in the kindlin-2+/− mice. RM1 prostate tumors grown in kindlin-2+/− mice had fewer blood vessels, which were thinner and shorter and supported less tumor growth compared with wild-type littermates. The vessels that did form in the kindlin-2+/− mice lacked smooth muscle cells and pericytes and had thinner basement membranes, indicative of immature vessels. VEGF-induced angiogenesis in matrigel implants was also abnormal in the kindlin-2+/− mice. Vessels in the kindlin-2+/− mice were leaky, and BM transplantation from kindlin-2+/− to WT mice did not correct this defect. Endothelial cells derived from kindlin-2+/− mice had integrin expression levels similar to WT mice but reduced αVβ3-dependent signaling, migration, adhesion, spreading, and tube formation. Developmental angiogenesis was markedly impaired by kindlin-2 morpholinos in zebrafish. Taken together, kindlin-2 plays an important role in pathologic and developmental angiogenesis, which arises from defective activation of integrin αVβ3.

Investigation into the metabolism of 1,8-cineole in an intestinal cell culture model and acquisition of its immune-modulatory effect via gene expression analysis

2012 ◽  
Vol 27 (6) ◽  
pp. 405-413 ◽  
Author(s):  
Jakob Müller ◽  
Natalie Gruner ◽  
Isabella Almstätter ◽  
Frauke Kirsch ◽  
Andrea Buettner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Intestinal Cell ◽  
Cell Culture Model ◽  
Culture Model

scholarly journals Temporal Gene Expression Analysis of Human Coronary Artery Endothelial Cells Treated With Simvastatin

2008 ◽  
Vol 14 (4) ◽  
pp. 229-239 ◽  
Author(s):  
LI QIN ZHANG ◽  
SHWU-FAN MA ◽  
DMITRY GRIGORYEV ◽  
TERA L. LAVOIE ◽  
HUI QING XIAO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Human Coronary Artery ◽  
Temporal Gene Expression
Sign in / Sign up

Export Citation Format

Share Document