Cirrhosis, a late form of liver disease, is characterized by extensive scarring due to exacerbated secretion of extracellular matrix proteins by myofibroblasts that develop during this process. These myofibroblasts arise mainly from hepatic stellate cells (HSCs), liver-specific pericytes that become activated at the onset of liver injury. Consequently, HSCs tend to be viewed mainly as myofibroblast precursors in a fibrotic process driven by inflammation. Here, the molecular interactions between liver pericytes and inflammatory cells such as macrophages and neutrophils at the first moments after injury and during the healing process are brought into focus. Data on HSCs and pericytes from other tissues indicate that these cells are able to sense pathogen- and damage-associated molecular patterns and have an important proinflammatory role in the initial stages of liver injury. On the other hand, further data suggest that as the healing process evolves, activated HSCs play a role in skewing the initial proinflammatory (M1) macrophage polarization by contributing to the emergence of alternatively activated, pro-regenerative (M2-like) macrophages. Finally, data suggesting that some HSCs activated during liver injury could behave as hepatic progenitor or stem cells will be discussed.
Keywords: Kupffer cells; hepatic stellate cells; inflammation; liver diseases; liver injury; macrophages; pericytes; perivascular cells.
Conflict of interest statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Cooperation of liver cells in health and disease.Adv Anat Embryol Cell Biol. 2001;161:III-XIII, 1-151. doi: 10.1007/978-3-642-56553-3. Adv Anat Embryol Cell Biol. 2001. PMID: 11729749 Review.
Hepatic stellate cells--the pericytes in the liver.Pflugers Arch. 2013 Jun;465(6):775-8. doi: 10.1007/s00424-012-1209-5. Epub 2013 Jan 5. Pflugers Arch. 2013. PMID: 23292551 Review.
Origin of myofibroblasts in the fibrotic liver in mice.Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):E3297-305. doi: 10.1073/pnas.1400062111. Epub 2014 Jul 29. Proc Natl Acad Sci U S A. 2014. PMID: 25074909 Free PMC article.
Hepatic stellate cells orchestrate clearance of necrotic cells in a hypoxia-inducible factor-1α-dependent manner by modulating macrophage phenotype in mice.J Immunol. 2014 Apr 15;192(8):3847-3857. doi: 10.4049/jimmunol.1303195. Epub 2014 Mar 17. J Immunol. 2014. PMID: 24639359 Free PMC article.
EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells.Sci Rep. 2018 Feb 7;8(1):2532. doi: 10.1038/s41598-018-20926-9. Sci Rep. 2018. PMID: 29416088 Free PMC article.
Cited by 1 article
The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond.Cells. 2020 Apr 22;9(4):1041. doi: 10.3390/cells9041041. Cells. 2020. PMID: 32331364 Free PMC article. Review.