Endothelial-to-Mesenchymal Transition in Cancer

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.

Download Full-text

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

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00277-6 ◽

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.

Download Full-text

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00074.2016 ◽

2016 ◽

Vol 310 (11) ◽

pp. L1185-L1198 ◽

Cited By ~ 12

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.

Download Full-text

Macrophages commit postnatal endothelium-derived progenitors to angiogenesis and restrict endothelial to mesenchymal transition during muscle regeneration

Cell Death and Disease ◽

10.1038/cddis.2013.558 ◽

2014 ◽

Vol 5 (1) ◽

pp. e1031-e1031 ◽

Cited By ~ 43

Author(s):

P Zordan ◽

E Rigamonti ◽

K Freudenberg ◽

V Conti ◽

E Azzoni ◽

...

Keyword(s):

Muscle Regeneration ◽

Mesenchymal Transition ◽

Endothelial To Mesenchymal Transition

Download Full-text

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

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa321 ◽

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

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms22158088 ◽

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.

Download Full-text

The Contribution of Endothelial-Mesenchymal Transition to Atherosclerosis

International Journal of Translational Medicine ◽

10.3390/ijtm1010004 ◽

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.

Download Full-text

Endothelial-to-Mesenchymal Transition in Human Adipose Tissue Vasculature Alters the Particulate Secretome and Induces Endothelial Dysfunction

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312826 ◽

2019 ◽

Vol 39 (10) ◽

pp. 2168-2191 ◽

Cited By ~ 3

Author(s):

Bronson A. Haynes ◽

Li Fang Yang ◽

Ryan W. Huyck ◽

Eric J. Lehrer ◽

Joshua M. Turner ◽

...

Keyword(s):

Adipose Tissue ◽

Endothelial Dysfunction ◽

Smooth Muscle Actin ◽

Phenotypic Change ◽

Alpha Smooth Muscle Actin ◽

Mesenchymal Transition ◽

Molecular Features ◽

Endothelial To Mesenchymal Transition

Objective: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-β (tumor growth factor-β), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. Conclusions: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.

Download Full-text