Role of Metabolism in Hepatic Stellate Cell Activation and Fibrogenesis

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2018 Nov 29

PMID 30483502

Citations 41

Authors

Wei Hou

Wing-Kin Syn

Affiliations

Soon will be listed here.

Abstract

Activation of hepatic stellate cell (HSC) involves the transition from a quiescent to a proliferative, migratory, and fibrogenic phenotype (i.e., myofibroblast), which is characteristic of liver fibrogenesis. Multiple cellular and molecular signals which contribute to HSC activation have been identified. This review specially focuses on the metabolic changes which impact on HSC activation and fibrogenesis.

Citing Articles

Interleukin 17A promotes glycolysis to activate human hepatic stellate cells by mediating the TRAF2/TRAF5/HuR/PFKFB3 axis.

Jiang T, Li S, Tang L, Tan Y, Ouyang W Cent Eur J Immunol. 2025; 49(4):404-424.

PMID: 39944257 PMC: 11811719. DOI: 10.5114/ceji.2024.145013.

Epitranscriptomic regulation of lipid oxidation and liver fibrosis via ENPP1 mRNA mA modification.

Sun F, Wang J, Yang Y, Dong Q, Jia L, Hu W Cell Mol Life Sci. 2024; 81(1):387.

PMID: 39249529 PMC: 11383905. DOI: 10.1007/s00018-024-05420-y.

Comprehensive evaluation of the mechanism of human adipose mesenchymal stem cells ameliorating liver fibrosis by transcriptomics and metabolomics analysis.

Ji G, Zhang Z, Wang X, Guo Q, Zhang E, Li C Sci Rep. 2024; 14(1):20035.

PMID: 39198546 PMC: 11358327. DOI: 10.1038/s41598-024-70281-1.

The effects of TGF-β-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells.

Wilhelmsen I, Combriat T, Dalmao-Fernandez A, Stokowiec J, Wang C, Olsen P Stem Cell Res Ther. 2024; 15(1):223.

PMID: 39044210 PMC: 11267759. DOI: 10.1186/s13287-024-03852-8.

Quercetin alleviates liver fibrosis via regulating glycolysis of liver sinusoidal endothelial cells and neutrophil infiltration.

Chen X, Wang Y, Wan J, Dou X, Zhang C, Sun M Biomol Biomed. 2024; 24(6):1806-1815.

PMID: 38943679 PMC: 11496877. DOI: 10.17305/bb.2024.10530.

References

She L, Xu D, Wang Z, Zhang Y, Wei Q, Aa J . Curcumin inhibits hepatic stellate cell activation via suppression of succinate-associated HIF-1α induction. Mol Cell Endocrinol. 2018; 476:129-138. DOI: 10.1016/j.mce.2018.05.002. View

Chong L, Hsu Y, Lee T, Lin Y, Chiu Y, Yang K . Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells. BMC Gastroenterol. 2015; 15:22. PMC: 4336504. DOI: 10.1186/s12876-015-0248-8. View

Glassner A, Eisenhardt M, Kramer B, Korner C, Coenen M, Sauerbruch T . NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner. Lab Invest. 2012; 92(7):967-77. DOI: 10.1038/labinvest.2012.54. View

Twu Y, Lee T, Lin Y, Hsu S, Wang Y, Liao C . Niemann-Pick Type C2 Protein Mediates Hepatic Stellate Cells Activation by Regulating Free Cholesterol Accumulation. Int J Mol Sci. 2016; 17(7). PMC: 4964497. DOI: 10.3390/ijms17071122. View

Wang W, Zhao C, Zhou J, Zhen Z, Wang Y, Shen C . Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in rats with non-alcoholic steatohepatitis-related liver fibrosis. PLoS One. 2013; 8(10):e76538. PMC: 3788732. DOI: 10.1371/journal.pone.0076538. View

Kurokawa T, Zheng Y, Ohkohchi N . Novel functions of platelets in the liver. J Gastroenterol Hepatol. 2015; 31(4):745-51. DOI: 10.1111/jgh.13244. View

Huang Y, Deng X, Liang J . Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017; 352(2):420-426. DOI: 10.1016/j.yexcr.2017.02.038. View

Tsuchida T, Friedman S . Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017; 14(7):397-411. DOI: 10.1038/nrgastro.2017.38. View

Mortezaee K . Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review. Cell Biochem Funct. 2018; 36(6):292-302. DOI: 10.1002/cbf.3351. View

10.

Li T, Eheim A, Klein S, Uschner F, Smith A, Brandon-Warner E . Novel role of nuclear receptor Rev-erbα in hepatic stellate cell activation: potential therapeutic target for liver injury. Hepatology. 2014; 59(6):2383-96. DOI: 10.1002/hep.27049. View

11.

El-Ashmawy N, El-Bahrawy H, Shamloula M, Ibrahim A . Antifibrotic effect of AT-1 blocker and statin in rats with hepatic fibrosis. Clin Exp Pharmacol Physiol. 2015; 42(9):979-987. DOI: 10.1111/1440-1681.12446. View

12.

Rangarajan S, Bone N, Zmijewska A, Jiang S, Park D, Bernard K . Metformin reverses established lung fibrosis in a bleomycin model. Nat Med. 2018; 24(8):1121-1127. PMC: 6081262. DOI: 10.1038/s41591-018-0087-6. View

13.

Trebicka J, Schierwagen R . Statins, Rho GTPases and KLF2: new mechanistic insight into liver fibrosis and portal hypertension. Gut. 2015; 64(9):1349-50. DOI: 10.1136/gutjnl-2014-308800. View

14.

Hyun J, Jung Y . MicroRNAs in liver fibrosis: Focusing on the interaction with hedgehog signaling. World J Gastroenterol. 2016; 22(29):6652-62. PMC: 4970468. DOI: 10.3748/wjg.v22.i29.6652. View

15.

Tuohetahuntila M, Spee B, Kruitwagen H, Wubbolts R, Brouwers J, van de Lest C . Role of long-chain acyl-CoA synthetase 4 in formation of polyunsaturated lipid species in hepatic stellate cells. Biochim Biophys Acta. 2014; 1851(2):220-30. DOI: 10.1016/j.bbalip.2014.12.003. View

16.

Palumbo-Zerr K, Zerr P, Distler A, Fliehr J, Mancuso R, Huang J . Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nat Med. 2015; 21(2):150-8. DOI: 10.1038/nm.3777. View

17.

Xie G, Wang X, Wang L, Wang L, Atkinson R, Kanel G . Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats. Gastroenterology. 2011; 142(4):918-927.e6. PMC: 3618963. DOI: 10.1053/j.gastro.2011.12.017. View

18.

Wang Y, Twu Y, Wang C, Lin F, Lee C, Liao Y . Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function. Int J Mol Sci. 2018; 19(6). PMC: 6032364. DOI: 10.3390/ijms19061678. View

19.

Lan T, Kisseleva T, Brenner D . Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation. PLoS One. 2015; 10(7):e0129743. PMC: 4519306. DOI: 10.1371/journal.pone.0129743. View

20.

Onal G, Kutlu O, Gozuacik D, Dokmeci Emre S . Lipid Droplets in Health and Disease. Lipids Health Dis. 2017; 16(1):128. PMC: 5492776. DOI: 10.1186/s12944-017-0521-7. View