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

Chen, Pei-Yu; Simons, Michael

doi:10.1097/mol.0000000000000542

Cited by 20 publications

(11 citation statements)

References 71 publications

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“…Thus, this TGFβ1-dependent paracrine restriction of retinal vasculature is mediated by microglia and occurs at the stiffest ONL, a mechanical boundary generally known to dictate collective tissue organization 46 . TGFβ1 and its signaling are associated with vascular pathologies, rather than development serving as a driver of endothelial-to-mesenchymal transition 47 . In the CNS, TGFβ1 mediates directed growth, differentiation, and anatomical orientation of axons 48 .…”

Section: Discussionmentioning

confidence: 99%

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

et al. 2020

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Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFβ1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFβ1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFβ1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFβ1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFβ1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS.

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Section: Discussionmentioning

confidence: 99%

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

et al. 2020

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“…Endothelial-to-mesenchymal transition (EndoMT) is characterized by the loss of EC features and the acquisition of mesenchymal, fibroblast, or stem cell-like characteristics, often initiated by the transforming growth factor b (TGF-b) family of ligands. Although required for normal heart valve development, deregulated EndoMT is also linked to pulmonary hypertension, vein graft failure, metastatic spread of tumors, atherosclerosis, and organ fibrosis (Chen and Simons, 2018). TGF-b signalinginduced EndoMT is accompanied by reduced FAO, which lowers cellular acetyl-CoA levels and SMAD7 acetylation and signaling (Figure 4D).…”

Section: Metabolic Regulation Of Ec Differentiation and Biology-metabolite Signalingmentioning

confidence: 99%

Hallmarks of Endothelial Cell Metabolism in Health and Disease

2019

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In 2009, it was postulated that endothelial cells (ECs) would only be able to execute the orders of growth factors if these cells would accordingly adapt their metabolism. Ten years later, it has become clear that ECs, often differently from other cell types, rely on distinct metabolic pathways to survive and form new blood vessels; that manipulation of EC metabolic pathways alone (even without changing angiogenic signaling) suffices to alter vessel sprouting; and that perturbations of these metabolic pathways can underlie excess formation of new blood vessels (angiogenesis) in cancer and ocular diseases. Initial proof of evidence has been provided that targeting (normalizing) these metabolic perturbations in diseased ECs and delivery of metabolites deserve increasing attention as novel therapeutic approaches for inhibiting or stimulating vessel growth in multiple disorders. Endothelial Metabolic Pathways Securing BioenergeticsCellular metabolism serves at least three main purposes, i.e., energy production, biomass synthesis, and redox homeostasis, in

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“…In addition to the Smad/non-Smad signaling pathway, TGFβ interacts with other signaling pathways that mediate and/or regulate EndMT, such as the Notch (Fu et al, 2009), fibroblast growth factor (FGF) (Chen and Simons, 2018), Wnt, and Sonic Hedgehog pathways (Horn et al, 2012). As such, Notch signaling is critical for heart formation during embryonic development (MacGrogan et al, 2018).…”

Section: Interplay With Other Signaling Pathways That Mediate or Regumentioning

confidence: 99%

TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering

Ma¹,

Sánchez‐Duffhues²,

Goumans³

et al. 2020

Front. Cell Dev. Biol.

179

129

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Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise to cells with multipotent potential. EndMT is essential for the formation of the cardiovascular system during embryonic development. Emerging results link EndMT to the postnatal onset and progression of fibrotic diseases and cancer. Moreover, recent reports have emphasized the potential for EndMT in tissue engineering and regenerative applications by regulating the differentiation status of cells. Transforming growth factor β (TGF-β) engages in many important physiological processes and is a potent inducer of EndMT. In this review, we first summarize the mechanisms of the TGF-β signaling pathway as it relates to EndMT. Thereafter, we discuss the pivotal role of TGF-β-induced EndMT in the development of cardiovascular diseases, fibrosis, and cancer, as well as the potential application of TGF-β-induced EndMT in tissue engineering.

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

Cited by 20 publications

References 71 publications

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics

Hallmarks of Endothelial Cell Metabolism in Health and Disease

TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering

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