scholarly journals Thymosin β4 reduces senescence of endothelial progenitor cells via the PI3K/Akt/eNOS signal transduction pathway

2012 ◽  
Vol 7 (2) ◽  
pp. 598-602 ◽  
Author(s):  
JUAN LI ◽  
FUYU QIU ◽  
LU YU ◽  
YANBO ZHAO ◽  
GUOSHENG FU ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Thymosin Β4 ◽  
Endothelial Progenitor

Fluid shear stress induces differentiation of circulating phenotype endothelial progenitor cells

2012 ◽  
Vol 303 (6) ◽  
pp. C595-C606 ◽  
Author(s):  
Syotaro Obi ◽  
Haruchika Masuda ◽  
Tomoko Shizuno ◽  
Atsuko Sato ◽  
Kimiko Yamamoto ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Signal Transduction Pathway ◽  
Tube Formation ◽  
Tissue Fluid ◽  
Transduction Pathway ◽  
Endothelial Progenitor

Endothelial progenitor cells (EPCs) are mobilized from bone marrow to peripheral blood, and contribute to angiogenesis in tissue. In the process, EPCs are exposed to shear stress generated by blood flow and tissue fluid flow. Our previous study showed that shear stress induces differentiation of mature EPCs in adhesive phenotype into mature endothelial cells and, moreover, arterial endothelial cells. In this study we investigated whether immature EPCs in a circulating phenotype differentiate into mature EPCs in response to shear stress. When floating-circulating phenotype EPCs derived from ex vivo expanded human cord blood were exposed to controlled levels of shear stress in a flow-loading device, the bioactivities of adhesion, migration, proliferation, antiapoptosis, tube formation, and differentiated type of EPC colony formation increased. The surface protein expression rate of the endothelial markers VEGF receptor 1 (VEGF-R1) and -2 (VEGF-R2), VE-cadherin, Tie2, VCAM1, integrin αv/β3, and E-selectin increased in shear-stressed EPCs. The VEGF-R1, VEGF-R2, VE-cadherin, and Tie2 protein increases were dependent on the magnitude of shear stress. The mRNA levels of VEGF-R1, VEGF-R2, VE-cadherin, Tie2, endothelial nitric oxide synthase, matrix metalloproteinase 9, and VEGF increased in shear-stressed EPCs. Inhibitor analysis showed that the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal transduction pathway is a potent activator of adhesion, proliferation, tube formation, and differentiation in response to shear stress. Western blot analysis revealed that shear stress activated the VEGF-R2 phosphorylation in a ligand-independent manner. These results indicate that shear stress increases differentiation, adhesion, migration, proliferation, antiapoptosis, and vasculogenesis of circulating phenotype EPCs by activation of VEGF-R2 and the PI3K/Akt/mTOR signal transduction pathway.

Abstract 204: Serine Threonine Kinase-35 Regulates Diabetes-induced Endothelial Progenitor Cells Dysfunction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Darukeshwara Joladarashi ◽  
Rajarajan A. Thandavarayan ◽  
Sahana Suresh Babu ◽  
Prince Jeyabal ◽  
Raj Kishore ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Progenitor Cells ◽  
Protein Kinases ◽  
Endothelial Progenitor Cells ◽  
High Glucose ◽  
Diabetic Mice ◽  
Serine Threonine Kinase ◽  
Endothelial Progenitor ◽  
Threonine Kinase

The completion of the sequencing of the human genome has revealed that up to ~20% of the human genes encode proteins involved in signal transduction. Among these, there are >500 protein kinases. Protein kinases play a central role in the intracellular signal transduction systems involved in cell proliferation, differentiation, metabolism, and other responses to external stimuli. Serine Threonine Kinase 35 (STK35), a novel kinase that binds to nuclear actin, has been shown to regulate important cellular functions such as cell migration, proliferation, survival, and angiogenesis. However, the role of STK35 in Endothelial Progenitor Cells (EPC) function and in cardiac regeneration under diabetic condition is unknown. The purpose of this study was to determine the role of STK35 in diabetes-induced EPC dysfunction. The expression of STK35 in response to high glucose was measured by RT-PCR. STK35 expression was assessed in myocardial tissue from both human patients and mice with diabetes. To enable detailed study of STK35 biological effects in EPCs, we performed loss-of-function experiments by STK35 inhibition in EPCs. EPC from bone marrow of mice and exposed to high glucose level, showed decreased STK35 expression (vs normoglycemia-treated cells). In addition, STK35 knockdown in EPCs reduces their migration and vascular tube formation. Moreover, STK35 knockdown in EPCs have shown decreased in the expression of proangiogenic cytokines and growth factors. Results from both diabetic human heart and diabetic mice heart have also shown lower STK35 expression as compared to respective non-diabetic hearts. Taken together, these data suggest that diabetes decreases STK35 expression in EPCc thereby impairs EPC function under diabetic condition. Our future studies will test whether ex-vivo STK35-overexpression in EPCs rescues diabetes-induced dysfunction and whether their transplantation into myocardium of diabetic mice promotes angiogenesis and cardiac repair after injury.

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