Defective Initiation of Liver Regeneration in Osteopontin-Deficient Mice after Partial Hepatectomy due to Insufficient Activation of IL-6/Stat3 Pathway

International Journal of Biological Sciences
Yankai WenXiaoni Kong

Abstract

The initial process in liver regeneration after partial hepatectomy involves the recruitment of immune cells and the release of cytokines. Osteopontin (OPN), a pro-inflammatory protein, plays critical roles in immune cell activation and migration. Although OPN has been implicated in the pathogenesis of many liver diseases, the role of OPN in liver regeneration remains obscure. In the present study, we found that serum and hepatic OPN protein levels were significantly elevated in wild-type (WT) mice after partial hepatectomy (PHx) and that bile ductal epithelia were the major cell source of hepatic OPN. Compared to WT mice, OPN knockout (KO) mice exhibited delayed liver regeneration after PHx. This delay in OPN(-/-) mice was attributed to impaired hepatic infiltration of macrophages and neutrophils, decreased serum and hepatic IL-6 levels, and blunted activation of macrophages after PHx. Furthermore, we demonstrate that the attenuated activation of macrophages is at least partially due to decreased hepatic and portal vein LPS levels in OPN(-/-) mice. In response to decreased IL-6 levels, the activation of signal transducer and transcription (Stat) 3 was reduced in hepatocytes of OPN(-/-) mice compared to WT mice after PHx. Conse...Continue Reading

Citations

May 8, 2018·Cellular & Molecular Immunology·Yankai WenXiaoni Kong
Aug 7, 2018·Expert Review of Molecular Diagnostics·Mitchell R McGill, Hartmut Jaeschke
Apr 29, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qing LiangKejia Wang
Oct 1, 2016·Oncotarget·Na Li, Jinlian Hua
May 5, 2020·Frontiers in Immunology·Zhao Shan, Cynthia Ju
Aug 6, 2019·Frontiers in Physiology·Sara ZafarniaWiltrud Lederle
Sep 24, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Gaiping WangCuifang Chang
Nov 27, 2020·Expert Review of Gastroenterology & Hepatology·David S Umbaugh, Hartmut Jaeschke
Oct 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahran SongSeung Gwan Lee
Sep 29, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhuolun SongNatalia Nieto
Mar 27, 2021·Cellular and Molecular Gastroenterology and Hepatology·Min XuYueqiu Gao
Nov 1, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Yanze YinQiang Xia

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Methods Mentioned

BETA
protein assay
electrophoresis
PCR
ELISA

Software Mentioned

Image Lab TM

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