Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration.

Scientific Reports
Konstantin DirscherlErik Schadde

Abstract

Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hyp...Continue Reading

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Citations

Aug 9, 2020·International Journal of Molecular Sciences·Chiara Corrado, Simona Fontana
Dec 3, 2020·Frontiers in Physiology·Johannes Robert FleischerLena-Christin Conradi
Nov 14, 2020·International Journal of Molecular Sciences·Shintaro YagiShinji Uemoto
Apr 29, 2021·Biological Chemistry·Linda Große-Segerath, Eckhard Lammert

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Datasets Mentioned

BETA
GSE131168

Methods Mentioned

BETA
dissection
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

ImageJ
GraphPad
Leica Application Suite X
Excel
Affymetrix GeneChip Expression Console
Image J
ZEN blue
DAVID

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