scholarly journals Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2

2013 ◽  
Vol 228 (8) ◽  
pp. 1774-1783 ◽  
Author(s):  
Izabela Chrobak ◽  
Stefania Lenna ◽  
Lukasz Stawski ◽  
Maria Trojanowska
2021 ◽  
Author(s):  
Qingyu Zhang ◽  
Tengqi Li ◽  
Zirong Li ◽  
Jike Lu ◽  
Xinjie Wu ◽  
...  

Abstract Background: Glucocorticoid could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head and the application of icariin showed a protective effect. However, the impact of autocrine exosomes during these processes is still to be confirmed.Methods: Exosomes were extracted from BMECs treated with hydrocortisone or hydrocortisone plus icariin by super-speed centrifugation; exosome-carried proteins were evaluated via BCA assay, Western blotting, protein array assay and Elisa test, while miRNA expression profile was assessed via high-throughput sequencing and confirmed by quantitative polymerase chain reaction (qPCR) to screen candidate molecules responsible for BMEC-Exo function. BMECs were incubated with and without exosomes before glucocorticoid intervention and then the impact of BMECs-derived exosomes on BMECs viability, apoptosis, migration, angiogenesis, and protein expression was further assessed by a series of functional assays. Results: Exosomes secreted by BMECs could ameliorate glucocorticoid-induced endothelial cellular injury, improve cell viability, decrease cell apoptosis, and promote cell migration and angiogenesis compared with the blank control. These effects of secreted exosomes could be reinforced by icariin intervention. Meanwhile, mechanism studies showed that expression level of eNOS, COX-2, and pERK were significantly increased while the cleaved caspase-3 level was decreased in BMECs after coculture with exosomes. Although icariin treatment would not significantly change the size and total protein content of BMECs-derived exosomes, expression of exosome-carried vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) was enhanced and numerous miRNAs involved in cell proliferation and apoptosis were up-regulated (e.g., hsa-miR-1469 and hsa-miR-133a-5p) or down-regulated (e.g., hsa-miR-10b-5p) (p < 0.05). 29 differentially expressed inflammatory factors were detected between the exosomes secreted by the Icariin-treated and the Model groups.Conclusion: To sum up, the present study indicates that autocrine exosomes could significantly improve glucocorticoid-induced injury of BMECs, partially mediated by activation of MAPK/ERK pathway and regulation of several inflammation/apoptosis/proliferation-associated proteins. Icariin intervention could reinforce these effects and may act as a promising drug for improving glucocorticoid-induced injury of BMECs. In vivo or animal studies are still required to better understand the function of BMEC-derived exosomes.


2021 ◽  
Vol 18 ◽  
Author(s):  
Juxuan Ruan ◽  
Lei Wang ◽  
Jiheng Dai ◽  
Jing Li ◽  
Ning Wang ◽  
...  

Objective: Angiogenesis led by brain microvascular endothelial cells (BMECs) contributes to the remission of brain injury after brain ischemia reperfusion. In this study, we investigated the effects of hydroxysafflor yellow A(HSYA) on angiogenesis of BMECs injured by OGD/R via SIRT1-HIF-1α-VEGFA signaling pathway. Methods: The OGD/R model of BMECs was established in vitro by OGD for 2h and reoxygenation for 24h. At first, the concentrations of vascular endothelial growth factor (VEGF), Angiopoietin (ang) and platelet-derived growth factor (PDGF) in supernatant were detected by ELISA, and the proteins expression of VEGFA, Ang-2 and PDGFB in BMECs were tested by western blot; the proliferation, adhesion, migration (scratch healing and transwell) and tube formation experiment of BMECs; the expression of CD31 and CD34 were tested by immunofluorescence staining. The levels of sirtuin1(SIRT1), hypoxia-inducible factor-1α (HIF-1α), VEGFA mRNA and protein were tested. Results: HSYA up-regulated the levels of VEGF, Ang and PDGF in the supernatant of BMECs under OGD/R, and the protein expression of VEGFA, Ang-2 and PDGFB were increased; HSYA could significantly alleviate the decrease of cell proliferation, adhesion, migration and tube formation ability of BMECs during OGD/R; HSYA enhanced the fluorescence intensity of CD31 and CD34 of BMECs during OGD/R; HSYA remarkably up-regulated the expression of SIRT1, HIF-1α, VEGFA mRNA and protein after OGD/R, and these increase decreased after SIRT1 was inhibited. Conclusion: SIRT1-HIF-1α-VEGFA signaling pathway is involved in HSYA improves angiogenesis of BMECs injured by OGD/R.


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