Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) has become a growing public health problem worldwide, yet its pathophysiology remains unclear. Liver sinusoidal endothelial cells (LSEC) have unique morphology and function, and play a critical role in liver homeostasis. Emerging literature implicates LSEC in many pathological processes in the liver, including metabolic dysregulation, inflammation, angiogenesis, and carcinogenesis. In this review, we highlight the current knowledge of the role of LSEC in each of the progressive phases of NASH pathophysiology (steatosis, inflammation, fibrosis, and the development of hepatocellular carcinoma). We discuss processes that have important roles in NASH progression including the detrimental transformation of LSEC called “capillarization”, production of inflammatory and profibrogenic mediators by LSEC as well as LSEC-mediated angiogenesis. The current review has a special emphasis on LSEC adhesion molecules, and their key role in the inflammatory response in NASH. Moreover, we discuss the pathogenic role of extracellular vesicles and their bioactive cargos in liver intercellular communication, inflammation, and fibrosis. Finally, we highlight LSEC-adhesion molecules and derived bioactive product as potential therapeutic targets for human NASH.

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Role of Differentiation of Liver Sinusoidal Endothelial Cells in Progression and Regression of Hepatic Fibrosis in Rats

Gastroenterology ◽

10.1053/j.gastro.2011.12.017 ◽

2012 ◽

Vol 142 (4) ◽

pp. 918-927.e6 ◽

Cited By ~ 170

Author(s):

Guanhua Xie ◽

Xiangdong Wang ◽

Lei Wang ◽

Lin Wang ◽

Roscoe D. Atkinson ◽

...

Keyword(s):

Endothelial Cells ◽

Hepatic Fibrosis ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells

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Significant Role of Liver Sinusoidal Endothelial Cells in Hepatic Uptake and Degradation of Naked Plasmid DNA After Intravenous Injection

Pharmaceutical Research ◽

10.1023/b:pham.0000033009.17594.e5 ◽

2004 ◽

Vol 21 (7) ◽

pp. 1223-1228 ◽

Cited By ~ 40

Author(s):

Jin Hisazumi ◽

Naoki Kobayashi ◽

Makiya Nishikawa ◽

Yoshinobu Takakura

Keyword(s):

Endothelial Cells ◽

Intravenous Injection ◽

Significant Role ◽

Plasmid Dna ◽

Hepatic Uptake ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells ◽

Naked Plasmid ◽

Naked Plasmid Dna

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The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells

Comparative Hepatology ◽

10.1186/1476-5926-7-4 ◽

2008 ◽

Vol 7 (1) ◽

Cited By ~ 39

Author(s):

Inigo Martinez ◽

Geir I Nedredal ◽

Cristina I Øie ◽

Alessandra Warren ◽

Oddmund Johansen ◽

...

Keyword(s):

Endothelial Cells ◽

Oxygen Tension ◽

Structure And Function ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells ◽

And Function ◽

Isolated Liver

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The critical role of Krüppel-like factors in kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00550.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. F259-F265 ◽

Cited By ~ 17

Author(s):

Sandeep K. Mallipattu ◽

Chelsea C. Estrada ◽

John C. He

Keyword(s):

Current Knowledge ◽

Critical Role ◽

Vital Role ◽

Glomerular Filtration Barrier ◽

Kidney Fibrosis ◽

Physiological Processes ◽

Filtration Barrier ◽

And Function ◽

Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

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Inhibition of liver sinusoidal endothelial cells in rats with hepatic fibrosis by injection of VEGF 165 via the inferior vena cava

10.21203/rs.3.rs-200465/v1 ◽

2021 ◽

Author(s):

Zhigang Sun ◽

Tianyi Dong ◽

Zhun Zhang ◽

Tiantian Wang ◽

Chenyu Zhang ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Endothelial Cells ◽

Liver Fibrosis ◽

Serum Level ◽

Basement Membranes ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells ◽

Transmission Electron

Abstract Background Although VEGF can maintain the normal phenotype of liver sinusoidal endothelial cells (LSECs), it has also been reported that VEGF exacerbates cirrhosis. The role of VEGF in the progression and recovery of cirrhosis has still remained controversial.Methods We established a cirrhotic rat model by thioacetamide that was used as drinking water; besides, 0, 1, 2, and 4 μg VEGF165 were then continuously injected into the rats. The serum level of hyaluronic acid was measured by ELISA at 0, 1, and 4 weeks, separately. Serum levels of ALT, AST, direct bilirubin, indirect bilirubin, and ALB were detected by an automatic biochemical analyzer. In addition, the levels of VEGF165, CD44, MMP9, MMP2, HIF-1α, and endothelin were detected by Western blotting. The expression level of CD44 in LSECs was detected by immunohistochemistry. Changes of fenestrations of LSECs and basement membranes of blood vessels were observed by transmission electron microscopy. Results With the increase of dosage and duration of VEGF treatment, the levels of liver function markers in the serum, the levels of CD44, HIF-1α, hydroxyproline and endothelin were significantly improved. With determination of the serum level of hydroxyproline in the blood, it was disclosed that the mentioned level was markedly decreased. In the Sirius Red staining, the stained red area was gradually reduced. Images captured by transmission electron microscopy also confirmed that the ultrastructure of LSECs tended to be normal.Conclusion VEGF165 can accelerate the resolution of liver fibrosis by promoting fenestration structure formation in LSECs, as well as promoting material exchange between sinusoids and hepatocytes. Our findings may provide a new insight for the study of the role of VEGF in liver fibrosis.

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Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome

Biological Chemistry ◽

10.1515/hsz-2016-0216 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1315-1333 ◽

Cited By ~ 28

Author(s):

Isabel Meininger ◽

Daniel Krappmann

Keyword(s):

Current Knowledge ◽

Inflammatory Diseases ◽

Critical Role ◽

Antigen Receptor ◽

Lymphocyte Activation ◽

Downstream Signaling ◽

Antigen Receptor Signaling ◽

Autoimmune And Inflammatory Diseases ◽

And Function

Abstract The CARMA1-BCL10-MALT1 (CBM) signalosome triggers canonical NF-κB signaling and lymphocyte activation upon antigen-receptor stimulation. Genetic studies in mice and the analysis of human immune pathologies unveiled a critical role of the CBM complex in adaptive immune responses. Great progress has been made in elucidating the fundamental mechanisms that dictate CBM assembly and disassembly. By bridging proximal antigen-receptor signaling to downstream signaling pathways, the CBM complex exerts a crucial scaffolding function. Moreover, the MALT1 subunit confers a unique proteolytic activity that is key for lymphocyte activation. Deregulated ‘chronic’ CBM signaling drives constitutive NF-κB signaling and MALT1 activation, which contribute to the development of autoimmune and inflammatory diseases as well as lymphomagenesis. Thus, the processes that govern CBM activation and function are promising targets for the treatment of immune disorders. Here, we summarize the current knowledge on the functions and mechanisms of CBM signaling in lymphocytes and how CBM deregulations contribute to aberrant signaling in malignant lymphomas.

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