scholarly journals Semaphorin 7A knockdown improves injury and prevents endothelial‑to‑mesenchymal transition in ox‑LDL‑induced HUVECs by regulating β1 integrin expression

2021 ◽  
Vol 22 (6) ◽  
Author(s):  
Xiaoying Song ◽  
Jing Meng ◽  
Guoliang Yan ◽  
Haihui Wang ◽  
Haitao Li ◽  
...  
Keyword(s):  
Β1 Integrin ◽  
Integrin Expression ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

scholarly journals Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer

2011 ◽  
Vol 22 (14) ◽  
pp. 2423-2435 ◽  
Author(s):  
Michael K. Wendt ◽  
Molly A. Taylor ◽  
Barbara J. Schiemann ◽  
William P. Schiemann
Keyword(s):  
Breast Cancer ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Three Dimensional ◽  
Transforming Growth Factor Β ◽  
Β1 Integrin ◽  
Integrin Expression ◽  
Mesenchymal Transition ◽  
Epithelial Cadherin ◽  
Cancer Dormancy

Reduced epithelial cadherin (E-cad) is a hallmark of invasive carcinomas that have acquired epithelial-mesenchymal transition (EMT) phenotypes. Here we show that down-regulated E-cad expression induced by transforming growth factor-β (TGF-β) and EMT preceded breast cancer outgrowth in three-dimensional (3D) organotypic assays and in the lungs of mice. Pharmacological inhibitors against focal adhesion kinase prevented metastatic outgrowth of newly seeded organoids, but not that of their fully established counterparts. Interrogating the D2-HAN (hyperplastic alveolar nodule) model of breast cancer dormancy and metastasis showed that dormant D2.OR cells produced branched organoid morphologies in 3D-cultures, and expressed robust quantities of E-cad that was uncoupled from regulation by TGF-β. In contrast, metastatic D2.A1 organoids were spherical and wholly lacked E-cad expression. Interestingly, D2.A1 cells engineered to re-express E-cad formed branched organoids, down-regulated β1 integrin expression, and failed to undergo metastatic outgrowth. The tumor-suppressing function of E-cad was inactivated by increased microenvironmental rigidity, and was not recapitulated by expression of an E-cad mutant lacking its extracellular domain. Twist expression, but not that of Snail, reinitiated metastatic outgrowth in dormant D2.OR cells. Our findings show that EMT and its down-regulated expression of E-cad circumvent breast cancer dormancy in part by facilitating β1 integrin expression necessary for metastatic outgrowth.

scholarly journals Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2282
Author(s):  
Valentina Masola ◽  
Mario Bonomini ◽  
Maurizio Onisto ◽  
Pietro Manuel Ferraro ◽  
Arduino Arduini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Viability ◽  
Biological Effects ◽  
Membrane Integrity ◽  
Glucose Content ◽  
Mesenchymal Transition ◽  
Low Glucose ◽  
Endothelial To Mesenchymal Transition ◽  
Osmotic Agents

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

scholarly journals Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Xianglin Hu ◽  
Zhengwang Sun ◽  
Fengfeng Li ◽  
Chaoyin Jiang ◽  
Wangjun Yan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heterotopic Ossification ◽  
Transforming Growth Factor ◽  
Burn Injury ◽  
Hypoxia Inducible Factor ◽  
Total Body Surface Area ◽  
Adaptive Immune System ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

AbstractBurn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-β1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

scholarly journals Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype

2016 ◽  
Vol 310 (11) ◽  
pp. L1185-L1198 ◽  
Author(s):  
Toshio Suzuki ◽  
Yuji Tada ◽  
Rintaro Nishimura ◽  
Takeshi Kawasaki ◽  
Ayumi Sekine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Endothelial Cells ◽  
Repair Process ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Oxidase Inhibition ◽  
Endothelial To Mesenchymal Transition

Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c- kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.

scholarly journals Noncoding RNAs as Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn’s Disease: The Path From Bench to Bedside

2020 ◽  
Author(s):  
Long-Yuan Zhou ◽  
Si-Nan Lin ◽  
Florian Rieder ◽  
Min-Hu Chen ◽  
Sheng-Hong Zhang ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Noncoding Rnas ◽  
Transforming Growth Factor Β ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Fibrotic Diseases ◽  
Endothelial To Mesenchymal Transition

Abstract Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-β/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding RNAs (ncRNAs) stands out in fibrotic diseases in that ncRNAs exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncRNAs, including the emerging long ncRNAs and circular RNAs, in intestinal fibrogenesis. Notably, the translational potential of ncRNAs as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: • Characteristics of ncRNAs and mechanisms of intestinal fibrogenesis • Wide participation of ncRNAs (especially the emerging long ncRNAs and circular RNAs) in intestinal fibrosis, including transforming growth factor-β signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling • Translational potential of ncRNAs in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs

scholarly journals LncRNA AERRIE Is Required for Sulfatase 1 Expression, but Not for Endothelial-to-Mesenchymal Transition

2021 ◽  
Vol 22 (15) ◽  
pp. 8088
Author(s):  
Tan Phát Pham ◽  
Anke S. van Bergen ◽  
Veerle Kremer ◽  
Simone F. Glaser ◽  
Stefanie Dimmeler ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Transcription Factors ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Inflammatory Signals ◽  
Pathological Conditions ◽  
Non Coding Rna ◽  
Endothelial To Mesenchymal Transition ◽  
Long Non Coding Rna

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.

scholarly journals The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis

2021 ◽  
Vol 1 (1) ◽  
pp. 39-54
Author(s):  
Jinyu Zhang ◽  
Stella C. Ogbu ◽  
Phillip R. Musich ◽  
Douglas P. Thewke ◽  
Zhiqiang Yao ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Vascular Inflammation ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Common Chronic Disease ◽  
Complex Process ◽  
Endothelial To Mesenchymal Transition ◽  
Key Pathways ◽  
Endothelial Mesenchymal Transition ◽  
Progression Of Atherosclerosis

Atherosclerosis is a chronic progressive condition in which the wall of the artery develops abnormalities and causes thickening of the blood vessels. The development of atherosclerosis is a complex process characterized by vascular inflammation and the growth of atherosclerotic plaques that eventually lead to compromised blood flow. The endothelial to mesenchymal transition (EndMT) is a phenomenon whereby endothelial cells lose their endothelial properties and acquire a mesenchymal phenotype similar to myofibroblast and smooth muscle cells. This process is considered a key contributor to the development and, importantly, the progression of atherosclerosis. Thus, therapeutically targeting the EndMT will provide a broad strategy to attenuate the development of atherosclerosis. Here, we review our current knowledge of EndMT in atherosclerosis including several key pathways such as hypoxia, TGF-β signaling, inflammation, and environmental factors during the development of atherosclerosis. In addition, we discuss several transgenic mouse models for studying atherosclerosis. Taken together, rapidly accelerating knowledge and continued studies promise further progress in preventing this common chronic disease.

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