The Role of Scar-Associated Macrophages in Liver Fibrosis
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v5i3.2780
Abstract
Liver fibrosis is a critical condition closely linked to liver cirrhosis and hepatocellular carcinoma, primarily due to the accumulation of extracellular matrix proteins produced by activated myofibroblasts during chronic liver injuries. Scar-associated Macrophages (SAMs), a recently identified subgroup of macrophages, play a pivotal role in facilitating the transition of hepatic stellate cells (HSCs) into activated myofibroblasts. Understanding the functions of SAMs could potentially uncover new therapeutic targets for treating liver fibrosis. This review synthesizes current knowledge on the origins of activated myofibroblasts and SAMs, the interactions between HSCs and SAMs,and the therapeutic targets associated SAMs in the progression of liver fibrosis.
Keywords
liver fibrosis, scar-associated macrophages, hepatic stellate cells, myofibroblasts
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[1]Kisseleva, T., Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 18, 151–166 (2021).
[2]Ramachandran, P., Dobie, R., Wilson-Kanamori, J.R. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512–518 (2019).
[3]Thomas Fabre et al. ,Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation.Sci. Immunol.8,eadd8945(2023).
[4]Kim, Hyun Young et al. The Origin and Fate of Liver Myofibroblasts. Cellular and molecular gastroenterology and hepatology vol. 17,1 (2024).
[5]Sun, Mengxi, and Tatiana Kisseleva. Reversibility of liver fibrosis. Clinics and research in hepatology and gastroenterology vol. 39 Suppl 1,0 1 (2015).
[6]Wu, B., Shentu, X., Nan, H. et al. A spatiotemporal atlas of cholestatic injury and repair in mice. Nat Genet 56, 938–952 (2024).
[7]Ehling, Josef et al. CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis. Gut vol. 63,12 (2014).
[8]Lendahl, U., Muhl, L. & Betsholtz, C. Identification, discrimination and heterogeneity of fibroblasts. Nat Commun 13, 3409 (2022).
[9]Biernacka, Anna et al. TGF-β signaling in fibrosis. Growth factors (Chur, Switzerland) vol. 29,5 (2011).
[10]Cheng, Sheng et al. Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis. MedComm vol. 4,5 e378. 17 Sep. 2023.
[11]de Gouville, A. C. et al. Inhibition of TGF-β signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br. J. Pharmacol.145,166–177 (2005).
[12]Meurer, S. K. et al. Overexpression of endoglin modulates TGF-beta1-signalling pathways in a novel immortalized mouse hepatic stellate cell line. PLoS ONE 8, e56116 (2013).
[13]Seki, E. et al. CCR2 promotes hepatic fibrosis in mice. Hepatology 50,185–197(2009).
[14]Qu, K. et al. New insight into the anti-liver fibrosis effect of multitargeted tyrosine kinase inhibitors: from molecular target to clinical trials. Front. Pharmacol. 6, 300 (2015).
[2]Ramachandran, P., Dobie, R., Wilson-Kanamori, J.R. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512–518 (2019).
[3]Thomas Fabre et al. ,Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation.Sci. Immunol.8,eadd8945(2023).
[4]Kim, Hyun Young et al. The Origin and Fate of Liver Myofibroblasts. Cellular and molecular gastroenterology and hepatology vol. 17,1 (2024).
[5]Sun, Mengxi, and Tatiana Kisseleva. Reversibility of liver fibrosis. Clinics and research in hepatology and gastroenterology vol. 39 Suppl 1,0 1 (2015).
[6]Wu, B., Shentu, X., Nan, H. et al. A spatiotemporal atlas of cholestatic injury and repair in mice. Nat Genet 56, 938–952 (2024).
[7]Ehling, Josef et al. CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis. Gut vol. 63,12 (2014).
[8]Lendahl, U., Muhl, L. & Betsholtz, C. Identification, discrimination and heterogeneity of fibroblasts. Nat Commun 13, 3409 (2022).
[9]Biernacka, Anna et al. TGF-β signaling in fibrosis. Growth factors (Chur, Switzerland) vol. 29,5 (2011).
[10]Cheng, Sheng et al. Single-cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis. MedComm vol. 4,5 e378. 17 Sep. 2023.
[11]de Gouville, A. C. et al. Inhibition of TGF-β signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br. J. Pharmacol.145,166–177 (2005).
[12]Meurer, S. K. et al. Overexpression of endoglin modulates TGF-beta1-signalling pathways in a novel immortalized mouse hepatic stellate cell line. PLoS ONE 8, e56116 (2013).
[13]Seki, E. et al. CCR2 promotes hepatic fibrosis in mice. Hepatology 50,185–197(2009).
[14]Qu, K. et al. New insight into the anti-liver fibrosis effect of multitargeted tyrosine kinase inhibitors: from molecular target to clinical trials. Front. Pharmacol. 6, 300 (2015).
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