Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

Park, Yang-Gyu; Choi, Jawun; Jung, Hye-Kang; Song, In Kyu; Shin, Yongwhan; Park, Sang-Youel; Seol, Jae‐Won

doi:10.3892/ijmm.2017.3108

Cited by 12 publications

(8 citation statements)

References 29 publications

(53 reference statements)

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“…Uterine angiogenesis and vascular remodeling are critical events during menstrual cycle and pregnancy 1,2 . In the secretory phase of the menstrual cycle, the uterus is receptive to the implantation of the blastocyst by increasing vasculature and blood flow as well as uterine secretions 3 .…”

Section: Introductionmentioning

confidence: 99%

poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA

et al. 2019

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Uterine angiogenesis and vascular remodeling play critical roles in determing the normal menstrual cycle and successful pregnancy. Poor uterine angiogenesis usually results in pregnancy failure. Protein O-fucosyltransferase 1 (poFUT1) is the key enzyme responsible for O-fucosylated glycan biosynthesis on glycoproteins. However, the dynamic expression and regulation of poFUT1 on the uterine angiogenesis and vascular remodeling remain unknown. Here, we showed that the enlargement of the vascular lumen in the secretory phase was greater than that in the proliferative phase of the uterine endometrium during menstrual cycle; whereas there was a narrower vessel lumen and fewer blood vessels in the decidua from miscarriage patients than in that from healthy pregnancy women. Additionally, the expression of poFUT1 was increased in the uterine endometrium during the secretory phase compared with that in the proliferation phase, and its expression was decreased in the uterus of miscarriage patients compared with that of the healthy pregnancy women. Using hESCs and a mouse model, we demonstrated that poFUT1 increased the Ofucosylation on uPA, and activated of the RhoA signaling pathway, thus facilitating uterine angiogenesis and vascular remodeling. We also provide evidence that poFUT1 promotes hESCs angiogenesis by the decreased stemness of hESCs. These findings reveal a new insight into the uterine angiogenesis and vascular remodeling. The study suggests that poFUT1 could be seen as a novel potential diagnostic and therapeutic target for miscarriage.

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Section: Introductionmentioning

confidence: 99%

poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA

et al. 2019

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“…In vitro results suggest that the expression of VEGFR-3 on BECs is dependent on fluid shear stress characteristics [ 217 ]. Importantly, in a mature lymphatic network, VEGFR-3 expression also differs among LECs exposed to different local flow characteristics [ 25 , 141 ].…”

Section: Importance Of Flow-induced Mechanical Forces In Lymphaticsmentioning

confidence: 99%

Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

Bálint

Jakus

2021

IJMS

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Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

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“… 72 Interestingly, evidence suggests the role of Vegfr3 as part of a mechanosensitive complex in blood vessel formation is ligand-independent, this is thought to be due to its ability to modulate Vegfr2 signalling. 73 VEGFR3 signalling can also be mediated through integrin/SRC; this however induces a different phosphorylation pattern to that induced by VEGFC and VEGFD. 74 This indicates ligand-independent functions for VEGFR3 and adds to the complexity of the VEGFR3 signalling system.…”

Section: Vascular Endothelial Growth Factor Receptors and Their Ligandsmentioning

confidence: 99%

The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases

Monaghan

Page

Østergaard

et al. 2020

Cardiovascular Research

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Vascular endothelial growth factor receptors (VEGFRs) are part of the evolutionarily conserved VEGF signalling pathways that regulate the development and maintenance of the body’s cardiovascular and lymphovascular systems. VEGFR3, encoded by the FLT4 gene, has an indispensable and well-characterised function in development and establishment of the lymphatic system. Autosomal dominant VEGFR3 mutations, that prevent the receptor functioning as a homodimer, cause one of the major forms of hereditary primary lymphoedema; Milroy disease. Recently, we and others have shown that FLT4 variants, distinct to those observed in Milroy disease cases, predispose individuals to Tetralogy of Fallot, the most common cyanotic congenital heart disease, demonstrating a novel function for VEGFR3 in early cardiac development. Here, we examine the familiar and emerging roles of VEGFR3 in the development of both lymphovascular and cardiovascular systems, respectively, compare how distinct genetic variants in FLT4 lead to two disparate human conditions, and highlight the research still required to fully understand this multifaceted receptor.

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Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

Cited by 12 publications

References 29 publications

poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA

poFUT1 promotes uterine angiogenesis and vascular remodeling via enhancing the O-fucosylation on uPA

Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases

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