Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Desroches-Castan, Agnès; Tillet, Emmanuelle; Ricard, Nicolas; Ouarné, Marie; Mallet, Christine; Feige, Jean‐Jacques; Bailly, Sabine

doi:10.3390/cells8091079

Cited by 29 publications

(33 citation statements)

References 45 publications

(80 reference statements)

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“…BMP9, which is produced by hepatic stellate cells, induces the fenestration of the sinusoidal endothelial cells 145 (Figs 1 , 2 ). Deletion of Bmp9 in 129/Ola mice triggers hepatic fibrosis following sinusoidal capillarization (transformation of the fenestrated hepatic sinusoids into continuous capillaries, with synthesis of a basement membrane of collagen between the endothelial cells and the hepatocytes) 146 (Table 1 ).…”

Section: Bmp Signallingmentioning

confidence: 99%

The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy

et al. 2021

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Endothelial cells are at the interface between circulating blood and tissues. This position confers on them a crucial role in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. The endothelium adopts a structure that is specific to the needs and function of each tissue and organ and is subject to tissue-specific signalling input. In adults, endothelial cells are quiescent, meaning that they are not proliferating. Quiescence was considered to be a state in which endothelial cells are not stimulated but are instead slumbering and awaiting activating signals. However, new evidence shows that quiescent endothelium is fully awake, that it constantly receives and initiates functionally important signalling inputs and that this state is actively regulated. Signalling pathways involved in the maintenance of functionally quiescent endothelia are starting to be identified and are a combination of endocrine, autocrine, paracrine and mechanical inputs. The paracrine pathways confer a microenvironment on the endothelial cells that is specific to the perfused organs and tissues. In this Review, we present the current knowledge of organ-specific signalling pathways involved in the maintenance of endothelial quiescence and the pathologies associated with their disruption. Linking organ-specific pathways and human vascular pathologies will pave the way towards the development of innovative preventive strategies and the identification of new therapeutic targets.

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Section: Bmp Signallingmentioning

confidence: 99%

The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy

et al. 2021

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“…However, their immature nature made them unable to develop fenestrae and maintain HSC quiescent [83]. Besides NO, Hedgehog (Hh) signaling has also been implicated in LSEC capillarization by regulating liver X receptor (LXR) and BMP9 among others [74][75][76][77][78][79]. Although previously suggested, studies using caveolin-1 knockout mice have demonstrated that caveolin-1 has been observed in fenestrae but it is not involved in capillarization [80,81].…”

Section: Loss Of Lsec Fenestraementioning

confidence: 99%

The Endothelium as a Driver of Liver Fibrosis and Regeneration

Lafoz

Ruart

Anton

et al. 2020

Cells

105

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Liver fibrosis is a common feature of sustained liver injury and represents a major public health problem worldwide. Fibrosis is an active research field and discoveries in the last years have contributed to the development of new antifibrotic drugs, although none of them have been approved yet. Liver sinusoidal endothelial cells (LSEC) are highly specialized endothelial cells localized at the interface between the blood and other liver cell types. They lack a basement membrane and display open channels (fenestrae), making them exceptionally permeable. LSEC are the first cells affected by any kind of liver injury orchestrating the liver response to damage. LSEC govern the regenerative process initiation, but aberrant LSEC activation in chronic liver injury induces fibrosis. LSEC are also main players in fibrosis resolution. They maintain liver homeostasis and keep hepatic stellate cell and Kupffer cell quiescence. After sustained hepatic injury, they lose their phenotype and protective properties, promoting angiogenesis and vasoconstriction and contributing to inflammation and fibrosis. Therefore, improving LSEC phenotype is a promising strategy to prevent liver injury progression and complications. This review focuses on changes occurring in LSEC after liver injury and their consequences on fibrosis progression, liver regeneration, and resolution. Finally, a synopsis of the available strategies for LSEC-specific targeting is provided.

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“…Plasma pharmacokinetic was obtained from fluorescence imaging and ICP-MS measurements after analyses through a noncompartment model (GraphPad Prism 7.00, GraphPad Software, La Jolla California USA).Noninvasive SWIR imaging on mice with vascular disorders. Generation of Bmp9-KO mice in the 129-P2/Ola-Hsd genetic background (named here for easiness 129/Ola) has been previously described9,10 . Briefly, Bmp9-KO mice in the C57BL/6 genetic background were obtained from Dr Se-Jin Lee (Johns Hopkins University, Baltimore, MD) and back-crossed for 10 generations with 129-P2/Ola-Hsd wild-type mice (Harlan France, Gannat, France).All animals experiments followed the institutional guidelines formulated by the European Community for the Use of Experimental Animals were approved by ethics committees (CEA ethic committee for animal breeding and Cometh38 for in vivo imaging) and the French Ministry of Research and Education.…”

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confidence: 99%

High-Resolution Shortwave Infrared Imaging of Vascular Disorders Using Gold Nanoclusters

Musnier

Wegner

et al. 2020

ACS Nano

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We synthesized a generation of water-soluble, atomically precise gold nanoclusters (Au NCs) with anisotropic surface containing short dithiol pegylated chain. These Au NCs exhibit a high brightness (QY∼6%) in the shortwave infrared (SWIR) spectrum with a detection above 1250nm and showed a slow elimination from blood with a weak accumulation in organs. We also developed a non-invasive, whole-body vascular imaging system in the SWIR window with high-resolution, benefiting from a series of Monte Carlo image processing of the images. The imaging process enabled to improve contrast by one order of magnitude and enhance by 54% the spatial resolution. After systemic administration of these nanoprobes in mice, we could quantify vessel complexity in depth (>4mm). Using Bmp9 deficient mice, we can detect very subtle vascular disorders noninvasively. The combination of these anisotropic surface charged gold nanoclusters plus an improved SWIR imaging device allows then a precise mapping at high resolution and in depth of the organization of the vascular network in live animals.

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Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Cited by 29 publications

References 45 publications

The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy

The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy

The Endothelium as a Driver of Liver Fibrosis and Regeneration

High-Resolution Shortwave Infrared Imaging of Vascular Disorders Using Gold Nanoclusters

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