Faculty Opinions recommendation of ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation.

2021 ◽  
Author(s):  
Malcolm Alison
Keyword(s):  
Hepatocyte Proliferation ◽  
Liver Zonation

scholarly journals Angiocrine signaling in the hepatic sinusoids in health and disease

2016 ◽  
Vol 311 (2) ◽  
pp. G246-G251 ◽  
Author(s):  
Enis Kostallari ◽  
Vijay H. Shah
Keyword(s):  
Endothelial Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Cell Types ◽  
Hepatocyte Proliferation ◽  
Liver Sinusoidal Endothelial Cells ◽  
Functional Changes ◽  
Liver Zonation ◽  
Health And Disease ◽  
Short Synthesis

The capillary network irrigating the liver is important not only for nutrient and oxygen delivery, but also for the signals distributed to other hepatic cell types necessary to maintain liver homeostasis. During development, endothelial cells are a key component in liver zonation. In adulthood, they maintain hepatic stellate cells and hepatocytes in quiescence. Their importance in pathobiology is highlighted in liver regeneration and chronic liver diseases, where they coordinate paracrine cell behavior. During regeneration, liver sinusoidal endothelial cells induce hepatocyte proliferation and angiogenesis. During fibrogenesis, they undergo morphological and functional changes, which are reflected by their role in hepatic stellate cell activation, inflammation, and distorted sinusoidal structure. Therapeutic strategies to target angiocrine signaling are in progress but are in the early stages. Here, we offer a short synthesis of recent studies on angiocrine signaling in liver homeostasis, regeneration, and fibrogenesis.

ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation

2021 ◽  
Author(s):  
Tianliang Sun ◽  
Stefano Annunziato ◽  
Sebastian Bergling ◽  
Caibin Sheng ◽  
Vanessa Orsini ◽  
...  
Keyword(s):  
Hepatocyte Proliferation ◽  
Liver Zonation

Hepatocyte proliferation after partial hepatectomy in absence of NF-κB activation

2001 ◽  
Vol 120 (5) ◽  
pp. A359-A359
Author(s):  
S LAURENT ◽  
C SEMPOUX ◽  
Y HORMANS ◽  
L LAMBOTTE
Keyword(s):  
Partial Hepatectomy ◽  
Hepatocyte Proliferation

scholarly journals Erratum: Corrigendum: The RSPO–LGR4/5–ZNRF3/RNF43 module controls liver zonation and size

2016 ◽  
Vol 18 (11) ◽  
pp. 1260-1260 ◽  
Author(s):  
Lara Planas-Paz ◽  
Vanessa Orsini ◽  
Luke Boulter ◽  
Diego Calabrese ◽  
Monika Pikiolek ◽  
...  
Keyword(s):  
Liver Zonation

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Keratin 7 expression in hepatic cholestatic diseases

2021 ◽  
Author(s):  
S. Sakellariou ◽  
C. Michaelides ◽  
T. Voulgaris ◽  
J. Vlachogiannakos ◽  
E. Manesis ◽  
...  
Keyword(s):  
Bile Duct ◽  
Inverse Correlation ◽  
Bile Duct Obstruction ◽  
Hepatocyte Proliferation ◽  
Primary Biliary Cholangitis ◽  
Specific Marker ◽  
Ductular Reaction ◽  
Duct Obstruction ◽  
Cholestatic Diseases ◽  
Keratin 7

AbstractWe evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

LINC00265 maintains hepatocyte proliferation during liver regeneration by targeting miRNA-28-5p

2021 ◽  
Vol 85 (3) ◽  
pp. 528-536
Author(s):  
Sheng Yu ◽  
Zhonglin Cui ◽  
Jie Zhou ◽  
Kai Wang ◽  
Qingping Li ◽  
...  
Keyword(s):  
Liver Resection ◽  
Liver Regeneration ◽  
Therapeutic Option ◽  
Weight Ratio ◽  
Hepatocyte Proliferation ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Hepatocyte Regeneration ◽  
M Phase ◽  
Reporter Assays

ABSTRACT Long noncoding RNAs have been implicated in many biological processes, but their roles in liver regeneration still need to be illustrated. Therefore, we aimed to investigate the role of LINC00265 as a pivotal regulator of hepatocyte proliferation during liver regeneration. It was found that LINC00265 is significantly upregulated in rat liver tissues at various time points after 2/3 liver resection. LINC00265 knockdown inhibited hepatocyte proliferation, induced cell apoptosis and led to G2/M phase cell cycle arrestment. In rats subjected to surgery, LINC00265 knockdown decreased liver/body weight ratio, attenuated improvement from liver damage and reduced Ki67 and PCNA expression. Luciferase reporter assays confirmed that miR-28-5p was a direct target of LINC00265, and inhibition of miR-28-5p abolished the effect of LINC00265 knockdown. In summary, LINC00265 might maintain hepatocyte proliferation by targeting miR-28-5p during liver regeneration and should be considered as a promising therapeutic option for hepatocyte regeneration after liver resection.

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