Key role of liver sinusoidal endothelial cells in liver fibrosis

Xu, Mingxing; Zou, Yong; Zhong, Yi

doi:10.5582/bst.2017.01007

Cited by 30 publications

(25 citation statements)

References 65 publications

(63 reference statements)

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“…On the other hand, hepatic sinusoidal capillarization characterized by LSE transformation into the continuous vascular type, lack of LSEC fenestration and the formation of an organized basement membrane not only precedes fibrosis, but also promotes HSC activation and fibrosis [22,23,29]. Interestingly, the capillarization of sinusoids, commonly observed in cirrhosis, and well described in patients with primary biliary cirrhosis/cholangitis [28,29,30,38] was also reported by Xu et al in adult patients with AIH [9]. A B…”

Section: Discussionmentioning

confidence: 59%

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Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Łotowska¹,

Sobaniec-Łotowska²,

Sobaniec³

et al. 2018

pjp

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The pathogenesis of autoimmune hepatitis (AIH) is poorly understood. Up to now, little is known of the involvement of liver sinusoidal endothelial cells (LSECs), accounting for approximately 40% of nonparenchymal hepatic cells, in AIH morphogenesis in pediatric patients. The study objective was ultrastructural analysis of LSECs from pretreatment biopsies of 19 children, aged 4-17 years (14 girls), with clinically and histologically diagnosed AIH. Our study is the first to describe alterations in LSECs, from swelling to necrosis, demonstrating their important role in the morphogenesis and progression of pediatric AIH. Frequently damage to LSECs coexisted with significantly activated Kupffer cells, fibrogenesis and fibrosis, but not cirrhosis, accompanied by the appearance of transitional hepatic stellate cells. Interestingly, even though in half of the AIH children the sinusoidal vessels were found to undergo transformation of discontinuous into continuous endothelium showing features of defenestration, the true basement membrane did not form underneath. The fact that the basement membrane is not formed, even when LSECs are markedly damaged, may seem to indicate some regenerative capacities of these cells and lesion reversibility.

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Section: Discussionmentioning

confidence: 59%

“…Thus, we failed to notice distinct morphological transformation of LSECs into vascular-type endothelial cells. It should be taken into consideration that the LSEC defenestration itself and loss of protective properties, as indicated by other authors, is an early event preceding the initiation of perivascular fibrosis [22,23,25,29,38].…”

Section: Discussionmentioning

confidence: 86%

Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Łotowska¹,

Sobaniec-Łotowska²,

Sobaniec³

et al. 2018

pjp

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“…Fenestrations are their most significant morphological feature, but can only be visualized by scanning electron microscopy [20]. In normal liver, differentiated LSECs form capillaries of microvasculature and facilitate filtration by fenestrae as a selectively permeable barrier between liver parenchyma and sinusoid [21,22].…”

Section: Discussionmentioning

confidence: 99%

Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells Capillarization in Carbon Tetrachloride-Induced Rats Fibrosis.

Zhang

Liu

Zheng

et al. 2020

Preprint

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Background: Qizhu granule, a traditional Chinese medicine, has been widely used in clinic as a complementary and alternative medicine to treat liver fibrosis.However, the mechanism underlying its anti-hepatic fibrosis is still not clear. Liver fibrosis accompanied by liver sinusoidal pathological angiogenesis has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. In this study, we investigated the mechanism of anti-capillarization of this herbal drug against liver fibrosis.Materials and methods: The liver fibrosis rats model induced by 4-week of intervention with 40% CCl4 was employed in this study. Meanwhile, low, medium and high dose serum containing Qizhu granules were prepared. Liver tissues were acquired, and liver samples were subjected to histological studies.LSECs were isolated from liver fibrosis rats and were routinely cultured for 48h in low, medium and high dose of Qizhu granules-containing serum. The fenestration of LSECs in liver fibrosis rats were observed under scanning electron microscopy. The expression of the endothelial cell surface markers CD31, SE-1 and LSECs integrin ɑVβ3, FAK, p-FAK, Ras, MAPK, p-MAPK were measured by western blot.Results: Compared with the control group, the loss of fenestration of LSECs in the model group increased. After intervention of Qizhu granule-containing serum, the fenestration of the structure of LSECs in liver fibrosis induced by CCl4 increased, especially in the high-dose Qizhu granules group. ompared with the control group, the expression levels of SE-1 and CD31 in LSECs in the model group were significantly increased (P < 0.05). Compared with the model group, the expression levels of SE-1 and CD31 in LSECs of rats with hepatic fibrosis induced by CCl4 decreased after the treatment of low, medium and high dose serum containing Qizhu granules (P < 0.05). Among them, the expression levels of SE-1 and CD31 in LSECs of Qizhu granules group decreased with the increase of dosage, showing a dose-dependent relationship to a certain extent. Compared with the normal control group, the expression of integrin ɑVβ3, Ras, p-FAK and p-MAPK protein increased in the LSECs of model group(P <0.05). After treatment with Qizhu granule-containing serum, the expression of integrin ɑVβ3, p-FAK and p-MAPK protein in LSECs of liver fibrosis rats induced by CCl4 were reduced (P <0.05), and the expression of FAK, Ras and MAPK protein decreased ( P> 0.05).Conclusions: Qizhu granule could reduce the loss of fenestration of LSECs, transforming the cell phenotype of LSECs, and ameliorating the pathological remodeling of hepatic sinus capillarization in hepatic fibrosis induced by CCl4 in rats. It was found that Qizhu granules played an anti-fibrosis role by suppressing the expression of integrin ɑVβ3-FAK-Ras/MAPK signaling pathway of LSECs in CCl4-induced fibrosis rats.

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“…They are functionally unique because of the high activity of receptor-mediated endocytosis, which enables them to clear colloids and soluble waste macromolecules from circulation. 36 LSECs have long been noted to contribute to liver regeneration after liver injury. That is, there is crosstalk between HSCs and LSECs when the activation of HSCs https://doi.org/10.3350/cmh.2019.0022n and the formation of fibrosis occur.…”

Section: Liver Sinusoidal Endothelial Cells (Lsecs)mentioning

confidence: 99%

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

Chen

Xiao

2020

Clin Mol Hepatol

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End-stage liver disease is one of the leading causes of death around the world. Since insufficient sources of transplantable liver and possible immune rejection severely hinder the wide application of conventional liver transplantation therapy, artificial three-dimensional (3D) liver culture and assembly from stem cells have become a new hope for patients with end-stage liver diseases, such as cirrhosis and liver cancer. However, the induced differentiation of single-layer or 3D-structured hepatocytes from stem cells cannot physiologically support essential liver functions due to the lack of formation of blood vessels, immune regulation, storage of vitamins, and other vital hepatic activities. Thus, there is emerging evidence showing that 3D organogenesis of artificial vascularized liver tissue from combined hepatic cell types derived from differentiated stem cells is practical for the treatment of end-stage liver diseases. The optimization of novel biomaterials, such as decellularized matrices and natural macromolecules, also strongly supports the organogenesis of 3D tissue with the desired complex structure. This review summarizes new research updates on novel differentiation protocols of stem cell-derived major hepatic cell types and the application of new supportive biomaterials. Future biological and clinical challenges of this concept are also discussed.

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Key role of liver sinusoidal endothelial cells in liver fibrosis

Cited by 30 publications

References 65 publications

Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells Capillarization in Carbon Tetrachloride-Induced Rats Fibrosis.

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

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Key role of liver sinusoidal endothelial cells in liver fibrosis

Cited by 30 publications

References 65 publications

Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Liver sinusoidal endothelial cells in morphogenesis of pediatric autoimmune hepatitis. Ultrastructural characteristics – a novel report

Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells&nbsp;Capillarization in Carbon Tetrachloride-Induced&nbsp;Rats&nbsp;Fibrosis.

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

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Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells Capillarization in Carbon Tetrachloride-Induced Rats Fibrosis.