CXC chemokines function as a rheostat for hepatocyte proliferation and liver regeneration

PloS One
Gregory C WilsonAlex B Lentsch

Abstract

Our previous in vitro studies have demonstrated dose-dependent effects of CXCR2 ligands on hepatocyte cell death and proliferation. In the current study, we sought to determine if CXCR2 ligand concentration is responsible for the divergent effects of these mediators on liver regeneration after ischemia/reperfusion injury and partial hepatectomy. Murine models of partial ischemia/reperfusion injury and hepatectomy were used to study the effect of CXCR2 ligands on liver regeneration. We found that hepatic expression of the CXCR2 ligands, macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC), was significantly increased after both I/R injury and partial hepatectomy. However, expression of these ligands after I/R injury was 30-100-fold greater than after hepatectomy. Interestingly, the same pattern of expression was found in ischemic versus non-ischemic liver lobes following I/R injury with expression significantly greater in the ischemic liver lobes. In both systems, lower ligand expression was associated with increased hepatocyte proliferation and liver regeneration in a CXCR2-dependent fashion. To confirm that these effects were related to ligand concentration, we administered exogenous MIP-2 and KC t...Continue Reading

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Citations

Aug 10, 2015·Journal of Hepatology·Hiroyuki NojimaAlex B Lentsch
Jan 20, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Takanori KonishiAlex B Lentsch
May 16, 2018·Proceedings of the National Academy of Sciences of the United States of America·Tao ZhouZhanjiang Liu
Sep 19, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Thiago Henrique Caldeira de OliveiraMauro Martins M Teixeira
Oct 12, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Takanori KonishiAlex B Lentsch
May 24, 2017·World Journal of Gastroenterology : WJG·Chao-Chao QinZhi Chen
Jan 24, 2021·Journal of Tissue Engineering and Regenerative Medicine·Yoshikatsu SaitohMasafumi Goto
May 13, 2021·Nature Reviews. Gastroenterology & Hepatology·Sheng CaoVijay H Shah
Sep 13, 2017·Gene Expression·Takanori Konishi, Alex B Lentsch

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
light microscopy

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