Indoxyl sulfate‐induced calcification of vascular smooth muscle cells via the PI3K/Akt/NF‐κB signaling pathway

2019 ◽  
Vol 82 (12) ◽  
pp. 2000-2006 ◽  
Author(s):  
Xin He ◽  
Hongli Jiang ◽  
Fanfan Gao ◽  
Shanshan Liang ◽  
Meng Wei ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Indoxyl Sulfate

CEMIP regulates the proliferation and migration of vascular smooth muscle cells in atherosclerosis through the WNT–beta-catenin signaling pathway

2020 ◽  
Vol 98 (2) ◽  
pp. 249-257
Author(s):  
Qiang Xue ◽  
Xiaoli Wang ◽  
Xiaohui Deng ◽  
Yue Huang ◽  
Wei Tian
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
And Migration ◽  
Proliferation And Migration

In this study we investigated the regulatory role of cell-migration-inducing and hyaluronan-binding protein (CEMIP) in the proliferation and migration of vascular smooth muscle cells (VSMCs). The mRNA and protein levels of CEMIP were upregulated in the plasma samples from patients with atherosclerosis, and in VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB), compared with plasma from healthy subjects and untreated VSMCs. Silencing CEMIP suppressed PDGF-BB-induced cell migration and proliferation in VSMCs, as determined using a Cell Counting Kit-8 assays, 5-ethynyl-2′-deocyuridine (EDU) assays, flow cytometry, wound healing assays, and Transwell assays. Overexpression of CEMIP promoted the proliferation and migration of VSMCs via activation of the Wnt–β-catenin signaling pathway and the upregulation of its target genes, including matrix metalloproteinase-2, matrix metalloproteinase-7, cyclin D1, and c-myc, whereas CEMIP deficiency showed the opposite effects. The knockdown of CEMIP in ApoE−/− mice by intravenous injection of lentiviral vector expressing si-CEMIP protected against high-fat-diet-induced atherosclerosis, as shown by the reduced aortic lesion areas, aortic sinus lesion areas, and the concentration of blood lipids compared with mice normally expressing CEMIP. These results demonstrated that CEMIP regulates the proliferation and migration of VSMCs in atherosclerosis by activating the WNT–β-catenin signaling pathway, which suggests the therapeutic potential of CEMIP for the management of atherosclerosis.

scholarly journals Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells

2017 ◽  
Vol 41 (5) ◽  
pp. 1894-1904 ◽  
Author(s):  
Sherin Samuel ◽  
Kuo Zhang ◽  
Yi-Da Tang ◽  
A. Martin Gerdes ◽  
Maria Alicia Carrillo-Sepulveda
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
No Production ◽  
Vascular Relaxation ◽  
Functional Studies

Background/Aims: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.

scholarly journals Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway

2015 ◽  
Vol 35 (3) ◽  
pp. 1151-1166 ◽  
Author(s):  
Cheng-wei Jin ◽  
Hui Wang ◽  
Yan-qing Chen ◽  
Meng-xiong Tang ◽  
Guan-qi Fan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Vascular Smooth Muscle Cells ◽  
Cellular Senescence ◽  
Replicative Senescence ◽  
Muscle Cells ◽  
Specific Protein ◽  
Foxo Signaling Pathway

Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.

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