scholarly journals Resolvin D1 Suppresses H2O2-Induced Senescence in Fibroblasts by Inducing Autophagy through the miR-1299/ARG2/ARL1 Axis

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1924
Author(s):  
Hyun Ji Kim ◽  
Boram Kim ◽  
Hyung Jung Byun ◽  
Lu Yu ◽  
Tuan Minh Nguyen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cellular Senescence ◽  
Vascular Endothelial Cells ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Dermal Fibroblasts ◽  
Vascular Endothelial ◽  
Yeast Two Hybrid ◽  
Resolvin D1 ◽  
Two Hybrid

ARG2 has been reported to inhibit autophagy in vascular endothelial cells and keratinocytes. However, studies of its mechanism of action, its role in skin fibroblasts, and the possibility of promoting autophagy and inhibiting cellular senescence through ARG2 inhibition are lacking. We induced cellular senescence in dermal fibroblasts by using H2O2. H2O2-induced fibroblast senescence was inhibited upon ARG2 knockdown and promoted upon ARG2 overexpression. The microRNA miR-1299 suppressed ARG2 expression, thereby inhibiting fibroblast senescence, and miR-1299 inhibitors promoted dermal fibroblast senescence by upregulating ARG2. Using yeast two-hybrid assay, we found that ARG2 binds to ARL1. ARL1 knockdown inhibited autophagy and ARL1 overexpression promoted it. Resolvin D1 (RvD1) suppressed ARG2 expression and cellular senescence. These data indicate that ARG2 stimulates dermal fibroblast cell senescence by inhibiting autophagy after interacting with ARL1. In addition, RvD1 appears to promote autophagy and inhibit dermal fibroblast senescence by inhibiting ARG2 expression. Taken together, the miR-1299/ARG2/ARL1 axis emerges as a novel mechanism of the ARG2-induced inhibition of autophagy. Furthermore, these results indicate that miR-1299 and pro-resolving lipids, including RvD1, are likely involved in inhibiting cellular senescence by inducing autophagy.

scholarly journals Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.

1987 ◽  
Vol 166 (5) ◽  
pp. 1390-1404 ◽  
Author(s):  
G Camussi ◽  
F Bussolino ◽  
G Salvidio ◽  
C Baglioni
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dermal Fibroblasts ◽  
Polymorphonuclear Neutrophils ◽  
Vascular Endothelial ◽  
Necrosis Factor

Murine tumor necrosis factor (mTNF) stimulates production of platelet-activating factor (PAF) by cultured rat peritoneal macrophages in amounts comparable to those formed during treatment with the calcium ionophore A23187 or phagocytosis of zymosan. The cell-associated PAF that was released into the medium was identical to synthetic PAF, as determined with physicochemical, chromatographic, and enzymatic assays. Furthermore, de novo synthesis of PAF by macrophages was demonstrated by the incorporation of radioactive precursors such as [3H]acetyl-coenzyme A or [3H]2-lyso-PAF. Macrophages incubated with mTNF for 4 h synthesized PAF only during the first h of treatment. At this time, the amount of cell-associated PAF was approximately equal to that released into the medium. The cell-associated PAF decreased afterwards, whereas that in the medium did not correspondingly increase, suggesting that some PAF was being degraded. The response of rat macrophages to different doses of mTNF and human TNF (hTNF) was examined. Maximal synthesis of PAF was obtained with 10 ng/ml of mTNF and 50 ng/ml of hTNF. This finding may be explained by a lower affinity of hTNF for TNF receptors of rat cells. The hTNF stimulated production of PAF by human vascular endothelial cells cultured from the umbilical cord vein. The time course of PAF synthesis was slower than that observed with macrophages, with maximal production between 4 and 6 h of treatment. Optimal synthesis of PAF was obtained with 10 ng/ml of hTNF. Only 20-30% of the PAF synthesized by endothelial cells was released into the medium, even after several hours of incubation. Synthesis of PAF in response to TNF was also detected in rat polymorphonuclear neutrophils, but not in human tumor cells and dermal fibroblasts. Therefore, production of PAF is a specialized response that is transient in macrophages continuously treated with TNF, and that appears to be controlled by unidentified regulatory mechanisms.

scholarly journals Resolvin D1 Reverts Lipopolysaccharide-Induced TJ Proteins Disruption and the Increase of Cellular Permeability by Regulating IκBαSignaling in Human Vascular Endothelial Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xingcai Zhang ◽  
Tingting Wang ◽  
Ping Gui ◽  
Chengye Yao ◽  
Wei Sun ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Vascular Endothelial Cells ◽  
Cell Permeability ◽  
Endothelial Barrier ◽  
Lipid Mediator ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Resolvin D1 ◽  
Cellular Permeability

Tight Junctions (TJ) are important components of paracellular pathways, and their destruction enhances vascular permeability. Resolvin D1 (RvD1) is a novel lipid mediator that has treatment effects on inflammatory diseases, but its effect on inflammation induced increase in vascular permeability is unclear. To understand whether RvD1 counteracts the lipopolysaccharide (LPS) induced increase in vascular cell permeability, we investigated the effects of RvD1 on endothelial barrier permeability and tight junction reorganization and expression in the presence or absence of LPS stimulation in cultured Human Vascular Endothelial Cells (HUVECs). Our results showed that RvD1 decreased LPS-induced increased in cellular permeability and inhibited the LPS-induced redistribution of zo-1, occludin, and F-actin in HUVECs. Moreover, RvD1 attenuated the expression of IκBαin LPS-induced HUVECs. The NF-κB inhibitor PDTC enhanced the protective effects of RvD1 on restoration of occludin rather than zo-1 expression in LPS-stimulated HUVECs. By contrast, the ERK1/2 inhibitor PD98059 had no effect on LPS-induced alterations in zo-1 and occludin protein expressions in HUVECs. Our data indicate that RvD1 protects against impairment of endothelial barrier function induced by LPS through upregulating the expression of TJ proteins in HUVECs, which involves the IκBαpathway but not the ERK1/2 signaling.

scholarly journals Effects of Rhein Lysinate on H2O2-induced cellular senescence of human umbilical vascular endothelial cells

2011 ◽  
Vol 32 (10) ◽  
pp. 1246-1252 ◽  
Author(s):  
Ya-jun Lin ◽  
Yong-zhan Zhen ◽  
Jie Wei ◽  
Bo Liu ◽  
Zong-yuan Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cellular Senescence ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Rhein Lysinate

scholarly journals Identification of a New Way to Induce Differentiation of Dermal Fibroblasts Into Vascular Endothelial Cells

2021 ◽  
Author(s):  
Xiaoling Cui ◽  
Jie Wen ◽  
Xiao Li ◽  
Nan Li ◽  
Xuxiao Hao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Vascular Function ◽  
Vascular Endothelial Cells ◽  
Dermal Fibroblasts ◽  
Angiogenic Factors ◽  
Immunofluorescent Staining ◽  
Vascular Endothelial ◽  
Qrt Pcr ◽  
Small Chemical

Abstract Background: Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is unclear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of dermal fibroblasts into vascular endothelial cells.Methods: In this study, dermal fibroblasts were treated with the different doses of CPP, and the mRNA level and protein level were detected by qPCR, Western blot and immunofluorescent staining. Matrigel assays also were used to teste the angiogenic ability of vascular endothelial cells derived from dermal fibroblasts.Results: Here, we report that a small chemical molecule, CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), efficiently induces the differentiation of dermal fibroblasts into Vascular endothelial cells. First, we observed that the morphology of CPP-treated dermal fibroblasts elongated, curved and formed circular patterns. Western blot and qRT-PCR analyses revealed that CPP effectively reduced the level of the dermal fibroblasts-marker Vimentin and increased levels of the vascular endothelial cells -markers CD31 and CD133. Detection of the percentage of CD31-positive cells from immunofluorescent staining confirmed that CPP efficiently induces dermal fibroblasts to differentiate into vascular endothelial cells. Matrigel assays showed that CPP-treated dermal fibroblasts have the functions of vascular endothelial cells. Western blot and qRT-PCR analyses of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB) showed that CPP induces dermal fibroblasts to vascular endothelial cells by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions: Our results indicate that the small chemical molecule CPP efficiently induces the differentiation of dermal fibroblasts into vascular endothelial cells. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.

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