scholarly journals Role of Endothelial-Mesenchymal Transition (EndoMT) in the Pathogenesis of Fibrotic Disorders

2011 ◽  
Vol 179 (3) ◽  
pp. 1074-1080 ◽  
Author(s):  
Sonsoles Piera-Velazquez ◽  
Zhaodong Li ◽  
Sergio A. Jimenez
Keyword(s):  
Mesenchymal Transition ◽  
Fibrotic Disorders ◽  
Endothelial Mesenchymal Transition

scholarly journals The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition

2020 ◽  
Vol 21 (16) ◽  
pp. 5875
Author(s):  
Katarzyna Sobierajska ◽  
Wojciech M. Ciszewski ◽  
Ewa Macierzynska-Piotrowska ◽  
Wanda Klopocka ◽  
Patrycja Przygodzka ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
In Silico Analysis ◽  
Dependent Manner ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Related Transcription Factor ◽  
Snail Family ◽  
Fibrotic Disorders ◽  
Endothelial Mesenchymal Transition

Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter’s regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process.

scholarly journals Endothelial-Mesenchymal Transition in Regenerative Medicine

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Damian Medici
Keyword(s):  
Stem Cell ◽  
Degenerative Diseases ◽  
Connective Tissues ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Mesenchymal Transition ◽  
Signaling Mechanisms ◽  
Recent Developments ◽  
Endothelial Mesenchymal Transition

Endothelial-mesenchymal transition (EndMT) is a fundamental cellular mechanism that regulates embryonic development and diseases such as cancer and fibrosis. Recent developments in biomedical research have shown remarkable potential to harness the EndMT process for tissue engineering and regeneration. As an alternative to traditional or artificial stem cell therapies, EndMT may represent a safe method for engineering new tissues to treat degenerative diseases by mimicking a process that occurs in nature. This review discusses the signaling mechanisms and therapeutic inhibitors of EndMT, as well as the role of EndMT in development, disease, acquiring stem cell properties and generating connective tissues, and its potential as a novel mechanism for tissue regeneration.

Downregulation of acylglycerol kinase suppresses high glucose-induced endothelial-mesenchymal transition in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway

2021 ◽  
Author(s):  
Haijing Wang ◽  
Zhuolei Feng ◽  
Xue Han ◽  
Yue Xing ◽  
Xiaomei Zhang
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
High Glucose ◽  
Notch Signaling Pathway ◽  
Mesenchymal Transition ◽  
Intrinsic Factors ◽  
Acylglycerol Kinase ◽  
Notch Pathways ◽  
Endothelial Mesenchymal Transition

The endothelial-mesenchymal transition (EndMT) participates in the progression of diabetic retinopathy (DR), but cell-intrinsic factors modulating this process remain elusive. In this study, we explored the role of lysophosphatidic acid (LPA)-producing enzyme, acylglycerol kinase (AGK) in the EndMT of human retinal microvascular endothelial cells (HRECs) under high glucose (HG) conditions. We found that AGK was significantly elevated in HG-treated cells. In addition, AGK knockdown reversed the HG-induced EndMT in HRECs, which was evidenced by the increased epithelial markers (CD31 and VE-cadherin) and decreased mesenchymal markers (FSP1 and α-SMA). Furthermore, downregulation of AGK inhibited the HG-induced activation of TGF-β/Notch pathways, whereas exogenous TGF-β1 (10 ng/ml) impeded the inhibitory effects of AGK knockdown on HG-induced EndMT in HRECs. Additionally, the silence of AGK abolished the HG-induced upregulation of LPA and its receptor LPAR1, and overexpression of LPAR1 further rescued the AGK knockdown-mediated inhibition of the EndMT process. In conclusion, we demonstrate that downregulation of acylglycerol kinase suppresses high glucose-induced endothelial-mesenchymal transition in HRECs through regulating the LPAR1/TGF-β/Notch signaling pathway, indicating that AGK might be a potential therapeutic target for the treatment of DR.

scholarly journals Engagement of circular RNA HECW2 in the nonautophagic role of ATG5 implicated in the endothelial-mesenchymal transition

Autophagy ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 404-418 ◽  
Author(s):  
Li Yang ◽  
Bing Han ◽  
Yuan Zhang ◽  
Ying Bai ◽  
Jie Chao ◽  
...  
Keyword(s):  
Circular Rna ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

scholarly journals Role of MCPIP1 in the Endothelial-Mesenchymal Transition Induced by Silica

2016 ◽  
Vol 40 (1-2) ◽  
pp. 309-325 ◽  
Author(s):  
Jie Chao ◽  
Xingang Wang ◽  
Yuxia Zhang ◽  
Tiebing Zhu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Umbilical Vein ◽  
Mesenchymal Cell ◽  
Akt Pathway ◽  
Mesenchymal Transition ◽  
Functional Changes ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Migration And Proliferation ◽  
Endothelial Mesenchymal Transition

Background: Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 µg/cm2). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis. Functional changes were evaluated by analyzing cell migration and proliferation. LC3-adenovirus transfections were performed, and changes in autophagy were measured using a marker of autophagy. Results: SiO2 induced decreases in the endothelial cell-specific markers in HUVECs while dramatically increasing mesenchymal cell product levels and mesenchymal functions. Although MCPIP1 expression increased in parallel with the increase in specific mesenchymal cell products, the MCPIP1 expression level was not consistent with the observed decrease in specific endothelial marker expression. Autophagy mediated the effects of MCPIP1, as rapamycin and 3-MA enhanced and attenuated the effect of SiO2 on HUVECs, respectively. MAPKs and the PI3K/Akt pathway were involved in the regulation of MCPIP1 by SiO2, and Pyk2 and MLC-2 mediated cell migration. Conclusion: Our findings reveal a new potential function of MCPIP1, suggesting a possible mechanism of fibrosis in pulmonary silicosis.

scholarly journals MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

2015 ◽  
Vol 309 (10) ◽  
pp. C680-C692 ◽  
Author(s):  
Sanjukta Chakraborty ◽  
David C. Zawieja ◽  
Michael J. Davis ◽  
Mariappan Muthuchamy
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fine Tuning ◽  
Vegf Receptor ◽  
Mesenchymal Transition ◽  
Factor Α ◽  
Endothelial Mesenchymal Transition ◽  
Necrosis Factor

The lymphatics have emerged as critical players in the progression and resolution of inflammation. The goal of this study was to identify specific microRNAs (miRNAs) that regulate lymphatic inflammatory processes. Rat mesenteric lymphatic endothelial cells (LECs) were exposed to the proinflammatory cytokine tumor necrosis factor-α for 2, 24, and 96 h, and miRNA profiling was carried out by real-time PCR arrays. Our data demonstrate a specific set of miRNAs that are differentially expressed (>1.8-fold and/or P < 0.05) in LECs in response to tumor necrosis factor-α and are involved in inflammation, angiogenesis, endothelial-mesenchymal transition, and cell proliferation and senescence. We further characterized the expression of miRNA 9 (miR-9) that was induced in LECs and in inflamed rat mesenteric lymphatics. Our results showed that miR-9 overexpression significantly repressed NF-κB expression and, thereby, suppressed inflammation but promoted LEC tube formation, as well as expression of the prolymphangiogenic molecules endothelial nitric oxide synthase and VEGF receptor type 3. LEC viability and proliferation and endothelial-mesenchymal transition were also significantly induced by miR-9. This study provides the first evidence of a distinct profile of miRNAs associated with LECs during inflammation. It also identifies the critical dual role of miR-9 in fine-tuning the balance between lymphatic inflammatory and lymphangiogenic pathways.

scholarly journals The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

2020 ◽  
Vol 8 ◽  
Author(s):  
Jacopo Di Gregorio ◽  
Iole Robuffo ◽  
Sonia Spalletta ◽  
Giulia Giambuzzi ◽  
Vincenzo De Iuliis ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Therapeutic Target ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Fibrotic Process ◽  
Fibrotic Disorders ◽  
The Relationship

Fibrosis is a chronic and progressive disorder characterized by excessive deposition of extracellular matrix, which leads to scarring and loss of function of the affected organ or tissue. Indeed, the fibrotic process affects a variety of organs and tissues, with specific molecular background. However, two common hallmarks are shared: the crucial role of the transforming growth factor-beta (TGF-β) and the involvement of the inflammation process, that is essential for initiating the fibrotic degeneration. TGF-β in particular but also other cytokines regulate the most common molecular mechanism at the basis of fibrosis, the Epithelial-to-Mesenchymal Transition (EMT). EMT has been extensively studied, but not yet fully explored as a possible therapeutic target for fibrosis. A deeper understanding of the crosstalk between fibrosis and EMT may represent an opportunity for the development of a broadly effective anti-fibrotic therapy. Here we report the evidences of the relationship between EMT and multi-organ fibrosis, and the possible therapeutic approaches that may be developed by exploiting this relationship.

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