Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny

Moonen, Jan-Renier; Krenning, Guido; Brinker, Marja G. L.; Koerts, Jasper; Luyn, Marja J. A. van; Harmsen, Martin C.

doi:10.1093/cvr/cvq012

Cited by 120 publications

(113 citation statements)

References 50 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…Endothelial cells that underwent EndMT lost the endothelial sprouting behavior (>60-fold reduction, P<0.001, Fig. 1L-O), corroborating functional alterations previously described during EndMT (Krenning et al, 2008;Moonen et al, 2010). Blockade of canonical TGFβ signaling with the small-molecule ALK5 inhibitor SB431542 inhibited these morphological, phenotypical and functional alterations (Fig.…”

Section: Tgfβ1 Induces Endothelial-mesenchymal Transition In An Alk5-supporting

confidence: 86%

“…Endothelial-mesenchymal transition (EndMT) is a process where endothelial cells lose their endothelial characteristics and start to differentiate into mesenchymal cells (Krenning et al, 2008Moonen et al, 2010;Maleszewska et al, 2013). EndMT is evidenced by the phenotypic and functional alteration of endothelial cells, which results in the repression of endothelial cell markers [e.g.…”

Section: Introductionmentioning

confidence: 99%

“…SM22α (also known as TAGLN) and αSMA (also known as ACTA2)] and acquirement of mesenchymal cell functions (i.e. contractile behavior and collagen production) (Krenning et al, 2008;Moonen et al, 2010;Maleszewska et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

FGF2 inhibits endothelial–mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-β signaling

Correia

Moonen

Brinker

et al. 2016

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Endothelial-to-mesenchymal transition (EndMT) is characterized by the loss of endothelial cell markers and functions, and coincides with de novo expression of mesenchymal markers. EndMT is induced by TGFβ1 and changes endothelial microRNA expression. We found that miR-20a is decreased during EndMT, and that ectopic expression of miR-20a inhibits EndMT induction. TGFβ1 induces cellular hypertrophy in human umbilical vein endothelial cells and abrogates VE-cadherin expression, reduces endothelial sprouting capacity and induces the expression of the mesenchymal marker SM22α (also known as TAGLN). We identified ALK5 (also known as TGFBR1), TGFBR2 and SARA (also known as ZFYVE9) as direct miR-20a targets. Expression of miR-20a mimics abrogate the endothelial responsiveness to TGFβ1, by decreasing ALK5, TGFBR2 and SARA, and inhibit EndMT, as indicated by the maintenance of VE-cadherin expression, the ability of the cells to sprout and the absence of SM22α expression. FGF2 increases miR-20a expression and inhibits EndMT in TGFβ1-stimulated endothelial cells. In summary, FGF2 controls endothelial TGFβ1 signaling by regulating ALK5, TGFBR2 and SARA expression through miR-20a. Loss of FGF2 signaling combined with a TGFβ1 challenge reduces miR-20a levels and increases endothelial responsiveness to TGFβ1 through elevated receptor complex levels and activation of Smad2 and Smad3, which culminates in EndMT.

show abstract

Section: Tgfβ1 Induces Endothelial-mesenchymal Transition In An Alk5-supporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FGF2 inhibits endothelial–mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-β signaling

Correia

Moonen

Brinker

et al. 2016

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…EndMT of the endothelial colony-forming cells resulted in the warning of endothelial markers, loss of endothelial functionality, and gain of mesenchymal marker expression and contractile function. The transdifferentiated cells harbored pro-angiogenic paracrine properties (11). Vascular support cells, such as pericytes and/or smooth muscle cells, may arise from the endothelium itself, and therefore, EndMT may be an important mechanism in recruiting such mural cells during angiogenesis.…”

Section: Endmt In Embryonic Developmentmentioning

confidence: 99%

The role of endothelial–mesenchymal transition in development and pathological process

2012

View full text Add to dashboard Cite

Epithelial–mesenchymal transition is an important developmental process, participates in tumor's formation, invasion, and metastasis and has been extensively studied. Recently, endothelial–mesenchymal transition (EndMT), a newly recognized type of cellular transdifferentiation, has been demonstrated to participate in a number of diseases by causing morphology changes and pathological processes. Previous studies showed that EndMT was a critical process of embryonic cardiac development. Not only that recent advances also suggested that EndMT occurred postnatally in cancer and cardiac fibrosis and emerged as a possible source of cancer‐associated fibroblasts (CAFs). CAFs were found to acquire properties that promoted tumor development and metastasis formation. Resident endothelial cells undergoing EndMT lose their endothelial markers, acquire a mesenchymal or myofibroblastic phenotype, express mesenchymal cell products such as α‐smooth muscle actin and type I collagen and develop invasive and migratory abilities. EndMT‐derived cells are believed to function as fibroblasts in damaged tissue and may therefore have an important role in pathological process. However, little is known about the signaling mechanisms that cause endothelial cells to transform into mesenchymal cells. Transforming growth factor‐β, Notch, or other signaling pathways could direct or interact to mediate EndMT. Therefore, to explore the signaling mechanisms of EndMT may provide novel therapeutic strategies for treating cancer. © 2012 IUBMB IUBMB Life, 64(9): 717–723, 2012.

show abstract

“…Furthermore, proteins that constitute the extracellular matrix (ECM), including fibronectin (FN), collagen type I and III, and vimentin are increased. [19][20][21][22] TGF-b binds its plasma membrane receptor, activin receptor-like kinase 5 (ALK5), to activate it and subsequently elicit intracellular signaling. 23,24 Several proteins that are involved in TGF-b intracellular signaling include the canonical pathway of phosphorylation of the family of Smad proteins and non-canonical intracellular pathways, to perform the activation of nuclear factor-kappa B (NF-kB).…”

mentioning

confidence: 99%

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Montorfano

Becerra

Cerro

et al. 2014

Laboratory Investigation

122

View full text Add to dashboard Cite

During the pathogenesis of systemic inflammation, reactive oxygen species (ROS) circulate in the bloodstream and interact with endothelial cells (ECs), increasing intracellular oxidative stress. Although endothelial dysfunction is crucial in the pathogenesis of systemic inflammation, little is known about the effects of oxidative stress on endothelial dysfunction. Oxidative stress induces several functions, including cellular transformation. A singular process of cell conversion is tendothelial-to-mesenchymal transition, in which ECs become myofibroblasts, thus losing their endothelial properties and gaining fibrotic behavior. However, the participation of oxidative stress as an inductor of conversion of ECs into myofibroblasts is not known. Thus, we studied the role played by oxidative stress in this conversion and investigated the underlying mechanism. Our results show that oxidative stress induces conversion of ECs into myofibroblasts through decreasing the levels of endothelial markers and increasing those of fibrotic and ECM proteins. The underlying mechanism depends on the ALK5/Smad3/NF-kB pathway. Oxidative stress induces the expression and secretion of TGF-b1 and TGF-b2 and p38 MAPK phosphorylation. Downregulation of TGF-b1 and TGF-b2 by siRNA technology abolished the H 2 O 2 -induced conversion. To our knowledge, this is the first report showing that oxidative stress is able to induce conversion of ECs into myofibroblasts via TGF-b secretion, emerging as a source for oxidative stress-based vascular dysfunction. Thus, oxidative stress emerges as a decisive factor in inducing conversion of ECs into myofibroblasts through a TGF-b-dependent mechanism, changing the ECs protein expression profile, and converting normal ECs into pathological ones. This information will be useful in designing new and improved therapeutic strategies against oxidative stress-mediated systemic inflammatory diseases.

show abstract

Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny

Abstract: Our study is the first to demonstrate that ECFCs can give rise to smooth muscle-like progeny, with potential therapeutic benefits. These findings further illustrate that ECFCs are highly plastic, which by itself has implications for therapeutical use.

Cited by 120 publications

References 50 publications

FGF2 inhibits endothelial–mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-β signaling

FGF2 inhibits endothelial–mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-β signaling

The role of endothelial–mesenchymal transition in development and pathological process

Oxidative stress mediates the conversion of endothelial cells into myofibroblasts via a TGF-β1 and TGF-β2-dependent pathway

Contact Info

Product

Resources

About