Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion

Abstract

Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-017-9563-8) contains supplementary material, which is available to authorized users.

RETRACTED ARTICLE: Sirtuin 3 inhibition induces mitochondrial stress in tongue cancer by targeting mitochondrial fission and the JNK-Fis1 biological axis

“…In colorectal cancer, knockdown of Sirt3 activates mitochondrial fission that initiates mitochondrial apoptosis in a manner dependent on caspase-9 (Wang et al 2018b). Sirt3 repression also impairs the amplification of mitochondrial DNA and consequently inhibits mitochondrial biogenesis (Turner et al 2017). In addition to the well-documented role of Sirt3 inhibition in mediating mitochondrial damage, exploring whether Sirt3 inhibition contributes to tongue cancer cell apoptosis via inducing mitochondrial stress is worthwhile.…”

Remodeling of the Microvasculature: May the Blood Flow Be With You

“…The co-existence of both remodeling processes can be envisioned in the entity called intussusceptive pruning in which pillar extension occurs in non-axial directions (Mentzer and Konerding, 2014); this has been observed in the extraembryonic vessels of chick embryos (Lee et al, 2011) and at the branch angles of bifurcating vessels in experimental mouse colitis (Ackermann et al, 2013). Moreover, reported images of the vascular plexus behind the sprouting front in the postnatal mouse retina show holes that could remind of intraluminal pillars (Turner et al, 2017), supporting the possible co-occurrence of both remodeling processes in this capillary plexus. Nevertheless, capillary splitting and pruning are still often considered independent and distinct processes.…”

Laminin-511 and α6 Integrins Regulate the Expression of CXCR4 to Promote Endothelial Morphogenesis

“…To determine whether the depletion of α6 integrins affected the surface expression of other integrins known to bind to laminin-511 and/or have been implicated in angiogenesis (Avraamides et al, 2008;Davis and Senger, 2005;Halann et al, 2005;Kortesmaa et al, 2000;Song et al, 2017;Turner et al, 2017), we analyzed the surface expression of α2, α3, and α5 subunits and the αvβ3 integrin in cells treated with non-targeting or α6 targeting siRNA by flow cytometry and compared the mean fluorescence intensity from three independent experiments ( Fig. 6).…”

“…Integrins are α/β heterodimeric receptors that bind to ECM proteins, including components of the basement membrane to mediate adhesion and to activate signaling pathways that cooperate with growth factor receptors to regulate cell behavior (Danen and Sonnenberg, 2003;Streuli and Akhtar, 2009). Several endothelial integrin heterodimers including α5β1, αvβ3, α2β1, and α6β1 are known to regulate angiogenesis [reviewed in (Avraamides et al, 2008;Davis and Senger, 2005) and their individual roles can be context dependent (Avraamides et al, 2008;Davis and Senger, 2005;Turner et al, 2017). Alpha 6 integrins are receptors for laminin-411 and laminin-511 (Hallmann et al, 2005;Kortesmaa et al, 2000).…”