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

Correia, Ana C. P.; Moonen, Jan-Renier; Brinker, Marja G. L.; Krenning, Guido

doi:10.1242/jcs.176248

Cited by 85 publications

(81 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to the roles of FGF-2 in preventing myofibroblast differentiation from epithelial cells, FGF-2 inhibits TGF-β-induced α-SMA expression in endothelial cells. FGF-2 prevents TGF-β-induced EndMT through the induction of miRNAs that target the TGF-β signal components, and through the activation of the MEK-Erk pathway that inhibits Smad2 phosphorylation [100][101][102].…”

Section: Cooperation With Diverse Signaling Pathways In Cancer-relatementioning

confidence: 99%

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

View full text Add to dashboard Cite

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

show abstract

Section: Cooperation With Diverse Signaling Pathways In Cancer-relatementioning

confidence: 99%

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Interestingly, an endothelial-specific knockout of either Fgfr1 or Frs2α increased neointima formation in transplant arteriopathy and atherosclerosis models due to induction of EndMT 17, 22 . Finally, FGF signaling also plays an important role in the maintenance of VEGFR2 expression and is required for the maintenance of both blood and lymphatic endothelial cells identity through FGF-Ras-MAPK signaling 31, 44–46 .…”

Section: Signaling Pathways Regulating Endmtmentioning

confidence: 99%

Fibroblast growth factor–transforming growth factor beta dialogues, endothelial cell to mesenchymal transition, and atherosclerosis

Chen

Simons

2018

Current Opinion in Lipidology

View full text Add to dashboard Cite

Purpose of review Despite much effort, atherosclerosis remains an important public health problem, leading to substantial morbidity and mortality worldwide. The purpose of this review is to provide an understanding of the role of endothelial cell fate change in atherosclerosis process. Recent findings Recent studies indicate that a process known as endothelial-to-mesenchymal transition (EndMT) may play an important role in atherosclerosis development. Transforming growth factor beta (TGFβ) has been shown to be an important driver of the endothelial cell phenotype transition. Summary The current review deals with the current state of knowledge regarding EndMT's role in atherosclerosis and its regulation by fibroblast growth factor (FGF)–TGFβ cross-talk. A better understanding of FGF–TGFβ signaling in the regulation of endothelial cell phenotypes is key to the development of novel therapeutic agents.

show abstract

“…Induction of miR-20a by FGF2 also depended on the activity of ERK, PI3K, and JNK, but not PLCγ nor p38. Knockdown of miR20a attenuated the ability of FGF2 to inhibit TGF-β-mediated endothelial to mesenchymal transition (EndMT) as evidenced by rescue of SMAD2/3 activation, rescue of SM22α, TGFβ-RI, and TGFβ-RII expression, and downregulation of VE-cadherin [76]. In mouse lens fiber cells, FGF2 has been determined to have a whole host of miRNA target genes, including genes encoding miRNAs that are involved in TGFβ, MAPK, integrin, and Wnt signaling pathways, among others, each of which has been implicated in fibrotic pathology [77].…”

Section: Evidence For Fgf2 As An Antagonist Of Myofibroblast Differenmentioning

confidence: 99%

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression

Dolivo

Larson

Dominko

2017

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

Fibrosis is a pathological condition that is characterized by the replacement of dead or damaged tissue with a nonfunctional, mechanically aberrant scar, and fibrotic pathologies account for nearly half of all deaths worldwide. The causes of fibrosis differ somewhat from tissue to tissue and pathology to pathology, but in general some of the cellular and molecular mechanisms remain constant regardless of the specific pathology in question. One of the common mechanisms underlying fibroses is the paradigm of the activated fibroblast, termed the “myofibroblast,” a differentiated mesenchymal cell with demonstrated contractile activity and a high rate of collagen deposition. Fibroblast growth factor 2 (FGF2), one of the members of the mammalian fibroblast growth factor family, is a cytokine with demonstrated antifibrotic activity in non-human animal, human, and in vitro models. FGF2 is highly pleiotropic and its receptors are present on many different cell types throughout the body, lending a great deal of variety to the potential mechanisms of FGF2 effects on fibrosis. However, recent reports demonstrate that a substantial contribution to the antifibrotic effects of FGF2 comes from the inhibitory effects of FGF2 on connective tissue fibroblasts, activated myofibroblasts, and myofibroblast progenitors. FGF2 demonstrates effects antagonistic towards fibroblast activation and towards mesenchymal transition of potential myofibroblast-forming cells, as well as promotes a gene expression paradigm more reminiscent of regenerative healing, such as that which occurs in the fetal wound healing response, than fibrotic resolution. With a better understanding of the mechanisms by which FGF2 alters the wound healing cascade and results in a shift away from scar formation and towards functional tissue regeneration, we may be able to further address the critical need of therapy for varied fibrotic pathologies across myriad tissue types.

show abstract

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

Cited by 85 publications

References 53 publications

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

Intracellular and extracellular TGF-β signaling in cancer: some recent topics

Fibroblast growth factor–transforming growth factor beta dialogues, endothelial cell to mesenchymal transition, and atherosclerosis

Fibroblast Growth Factor 2 as an Antifibrotic: Antagonism of Myofibroblast Differentiation and Suppression of Pro-Fibrotic Gene Expression

Contact Info

Product

Resources

About