Proapoptotic and survival signaling pathways plays a role in thrombospondin type I repeat mediated apoptosis in human microvascular endothelial cells

Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.

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TLR2 Ligand Pam3CSK4 Regulates MMP-2/9 Expression by MAPK/NF-κB Signaling Pathways in Primary Brain Microvascular Endothelial Cells

Neurochemical Research ◽

10.1007/s11064-018-2607-7 ◽

2018 ◽

Vol 43 (10) ◽

pp. 1897-1904 ◽

Cited By ~ 9

Author(s):

Hongyan Zhu ◽

Rongrong Dai ◽

Youquan Zhou ◽

Hao Fu ◽

Qiang Meng

Keyword(s):

Endothelial Cells ◽

Signaling Pathways ◽

Microvascular Endothelial Cells ◽

Brain Microvascular Endothelial Cells ◽

Tlr2 Ligand ◽

Microvascular Endothelial

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Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human Microvascular Endothelial Cells Through miR-195

Cellular Physiology and Biochemistry ◽

10.1159/000493454 ◽

2018 ◽

Vol 49 (4) ◽

pp. 1499-1511 ◽

Cited By ~ 13

Author(s):

Dexin Yin ◽

Changgeng Fu ◽

Dajun Sun

Keyword(s):

Endothelial Cells ◽

Cell Viability ◽

Signaling Pathways ◽

Western Blotting ◽

Tube Formation ◽

Mtor Signaling ◽

Microvascular Endothelial Cells ◽

Qrt Pcr ◽

Microvascular Endothelial ◽

Induced Apoptosis

Background/Aims: Recent studies have suggested that several lncRNAs contribute to the angiogenic function of endothelial cells. Herein, we set out to reveal whether lncRNA UCA1 has functions in endothelial angiogenesis. Methods: The expression levels of lncRNA UCA1, miR-195 and CCND1 in human microvascular endothelial HMEC-1 cells were altered by transfection. Subsequently, cell viability, migration, tube formation and apoptosis of HMEC-1 cells were respectively assessed. The cross-talk between lncRNA UCA1, miR-195, CCND1, and MEK/ERK and mTOR signaling pathways were investigated by performing qRT-PCR and Western blotting. Results: Silence of lncRNA UCA1 repressed HMEC-1 cells viability, migration, tube formation, and induced apoptosis. Meanwhile, silence of lncRNA UCA1 significantly up-regulated miR-195 expression. These alterations induced by lncRNA UCA1 were further enhanced by miR-195 overexpression, while were attenuated by miR-195 suppression. Moreover, silence of lncRNA UCA1 deactivated MEK/ERK and mTOR signaling pathways via a miR-195-dependent regulation. And the deactivation of MEK/ERK and mTOR signaling pathways led to a down-regulation of CCND1. Conclusion: This study demonstrates that silence of lncRNA UCA1 largely represses microvascular endothelial cells growth and tube formation. Silence of lncRNA UCA1 exerts its function possibly via up-regulation of miR-195, which in turn inactivates MEK/ERK and mTOR signaling pathways, and ultimately represses CCND1 expression.

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Fibrin and Collagen Differentially but Synergistically Regulate Sprout Angiogenesis of Human Dermal Microvascular Endothelial Cells in 3-Dimensional Matrix

International Journal of Cell Biology ◽

10.1155/2013/231279 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 45

Author(s):

Xiaodong Feng ◽

Marcia G. Tonnesen ◽

Shaker A. Mousa ◽

Richard A. F. Clark

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

Type I Collagen ◽

Three Dimensional ◽

Tumor Stroma ◽

Microvascular Endothelial Cells ◽

Type I ◽

Microvascular Endothelial

Angiogenesis is a highly regulated event involving complex, dynamic interactions between microvascular endothelial cells and extracellular matrix (ECM) proteins. Alteration of ECM composition and architecture is a hallmark feature of wound clot and tumor stroma. We previously reported that during angiogenesis, endothelial cell responses to growth factors are modulated by the compositional and mechanical properties of a surrounding three-dimensional (3D) extracellular matrix (ECM) that is dominated by either cross-linked fibrin or type I collagen. However, the role of 3D ECM in the regulation of angiogenesis associated with wound healing and tumor growth is not well defined. This study investigates the correlation of sprout angiogenesis and ECM microenvironment using in vivo and in vitro 3D angiogenesis models. It demonstrates that fibrin and type I collagen 3D matrices differentially but synergistically regulate sprout angiogenesis. Thus blocking both integrin alpha v beta 3 and integrin alpha 2 beta 1 might be a novel strategy to synergistically block sprout angiogenesis in solid tumors.

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