Bone morphogenetic protein-7 inhibits endothelial-to-mesenchymal transition in primary human umbilical vein endothelial cells and mouse model of systemic sclerosis via Akt/mTOR/p70S6K pathway

2021 ◽  
Author(s):  
Chen Shen ◽  
Ying Jiang ◽  
Qiao Li ◽  
Chaofan Liu ◽  
Feifei Hu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Mouse Model ◽  
Bone Morphogenetic Protein ◽  
Umbilical Vein ◽  
Bone Morphogenetic Protein 7 ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein ◽  
Endothelial To Mesenchymal Transition ◽  
Umbilical Vein Endothelial Cells

scholarly journals Ectopic transient overexpression of OCT-4 facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells

2020 ◽  
Vol 11 ◽  
pp. 204173142090920
Author(s):  
Seung Hyun L Kim ◽  
Seunghun S Lee ◽  
Inseon Kim ◽  
Janet Kwon ◽  
Song Kwon ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Endothelial Cells ◽  
Cell Therapy ◽  
Bone Morphogenetic Protein ◽  
Umbilical Vein ◽  
Cell Types ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
Umbilical Vein Endothelial Cells

Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.

scholarly journals CXCR7 Inhibits Fibrosis via Wnt/β-Catenin Pathways during the Process of Angiogenesis in Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
MinQian Shen ◽  
YiFan Feng ◽  
Jing Wang ◽  
YuanZhi Yuan ◽  
Fei Yuan
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Erk Signaling ◽  
Cell Type ◽  
Mesenchymal Transition ◽  
Human Umbilical Vein ◽  
Endothelial To Mesenchymal Transition ◽  
Umbilical Vein Endothelial Cells ◽  
Tissue Origin

Although SDF-1/CXCR7 plays an important role in angiogenesis, the function and the pathway of the SDF-1/CXCR7 axis might depend on the cell type or tissue origin and not fully understood. In this study, we investigated the effect of CXCR7 in SDF-1-induced proliferation, migration, apoptosis, tube formation, and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs), and the potential pathway of SDF-1/CXCR7. We confirmed that the silencing of CXCR7 inhibited the proliferation of HUVECs and contributed the apoptosis, while overexpressed CXCR7 increased SDF-1-induced HUVECs migration and tube formation. However, upregulated CXCR7 inhibited the expression of α-SMA, suggesting that CXCR7 might attenuate EndMT. In addition, overexpressed CXCR7 activated AKT and ERK signaling pathways but suppressed Wnt/β-catenin pathways in HUVECs. The inhibition of Wnt/β-catenin pathways decreased the expression of α-SMA. Altogether, these results suggest that CXCR7 might inhibit fibrosis via Wnt/β-catenin pathways during the process of angiogenesis.

scholarly journals MiR-200c-3p promotes ox-LDL-induced endothelial to mesenchymal transition in human umbilical vein endothelial cells through SMAD7/YAP pathway

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yongzhong Mao ◽  
Ling Jiang
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Rhodamine Phalloidin ◽  
Mesenchymal Transition ◽  
Human Umbilical Vein ◽  
Endothelial To Mesenchymal Transition ◽  
Umbilical Vein Endothelial Cells

Abstract Background Endothelial to mesenchymal transition (EndMT) participates in the progression of atherosclerosis (AS). MiR-200c-3p has been implicated in EndMT. However, the functional role of miR-200c-3p in AS remains largely unknown. Here, we demonstrated the critical role of miR-200c-3p in regulating EndMT in AS. Methods ApoE−/− mice were fed with high-fat diet to establish AS mouse model, and human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic AS cell model. The expression of miR-200c-3p, SMAD7 and YAP in ApoE−/− mice and HUVECs was detected by quantitative real-time PCR. Rhodamine phalloidin staining and Western blot were performed to observe cell morphology and EndMT marker expression of HUVECs. Luciferase reporter assay and Co-Immunoprecipitation were performed to verify the relationship among miR-200c-3p, SMAD7, and YAP. Results MiR-200c-3p was highly expressed, and SMAD7 and YAP were down-regulated in the aortic tissues of ApoE−/− mice and ox-LDL-treated HUVECs. MiR-200c-3p overexpression promoted the transformation of ox-LDL-treated HUVECs from cobblestone-like epithelial phenotype to a spindle-like mesenchymal phenotype. Meanwhile, miR-200c-3p up-regulation repressed the expression of endothelial markers CD31 and vWF and promoted the expression of mesenchymal markers α-SMA and vimentin in the ox-LDL-treated HUVECs. MiR-200c-3p inhibited SMAD7 and YAP expression by interacting with 3′ untranslated region of SMAD7. Moreover, miR-200c-3p promoted EndMT in ox-LDL-treated HUVECs by inhibiting SMAD7/YAP pathway. Conclusion This work demonstrated that MiR-200c-3p promoted ox-LDL-induced EndMT in HUVECs through SMAD7/YAP pathway, which may be important for the onset of atherosclerosis.

scholarly journals Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition

2019 ◽  
Vol 20 (3) ◽  
pp. 458 ◽  
Author(s):  
Fernanda Ursoli Ferreira ◽  
Lucas Eduardo Botelho Souza ◽  
Carolina Hassibe Thomé ◽  
Mariana Tomazini Pinto ◽  
Clarice Origassa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Transforming Growth Factor Β ◽  
Selective Inhibition ◽  
Mesenchymal Transition ◽  
Best Response ◽  
Endothelial To Mesenchymal Transition

The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor β (TGF-β) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-β2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs; primary aortic endothelial cells PAECs; human umbilical vein endothelia cells, HUVECs; and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal–regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation.

scholarly journals Liraglutide Inhibits Endothelial-to-Mesenchymal Transition and Attenuates Neointima Formation after Endovascular Injury in Streptozotocin-Induced Diabetic Mice

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 589 ◽  
Author(s):  
Tzu-Hsien Tsai ◽  
Chien-Ho Lee ◽  
Cheng-I Cheng ◽  
Yen-Nan Fang ◽  
Sheng-Ying Chung ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Morphological Changes ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Specific Marker ◽  
Neointima Formation ◽  
Diabetic Mice ◽  
Mesenchymal Transition ◽  
Compound C ◽  
Endothelial To Mesenchymal Transition

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

Sign in / Sign up

Export Citation Format

Share Document