中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 7
Jul.  2019
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Article Contents

Mechanism of action of hypoxia-inducible factor 1α in the development and progression of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2019.07.039
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  • Received Date: 2019-01-21
  • Published Date: 2019-07-20
  • Liver fibrosis and end-stage liver cirrhosis are often accompanied by liver hypoxia. As a key transcription factor for regulating the body's response to hypoxia, hypoxia-inducible factor 1α ( HIF-1α) plays an important role in the activation of hepatic stellate cells and the development and progression of liver fibrosis. In addition, downregulation of HIF-1α expression can alleviate liver fibrosis and thus HIF-1α is expected to become a new target for the treatment of liver fibrosis. This article reviews the association between HIF-1α and liver fibrosis-related signaling pathways and genes and further discusses the potential of HIF-1α as a new therapeutic target for liver fibrosis.

     

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  • [1]CANNITO S, PATERNOSTRO C, BUSLETTA C, et al.Hypoxia, hypoxia-inducible factors and fibrogenesis in chronic liver diseases[J].Histol Histopathol, 2014, 29 (1) :33-44.
    [2]ZHAO Y, MA X, WANG J, et al.Curcumin protects against CCl4-induced liver fibrosis in rats by inhibiting HIF-1αthrough an ERK-dependent pathway[J].Molecules, 2014, 19 (11) :18767-18780.
    [3]ZHAGN W, JIA JD.Pathogenesis and new therapeutic targets of liver fibrosis[J].J Clin Hepatol, 2017, 33 (3) :409-421. (in Chinese) 张伟, 贾继东.肝纤维化的发病机制及治疗新靶点[J].临床肝胆病杂志, 2017, 33 (3) :409-421.
    [4]HONG F, WAN L, LIU J, et al.Histone methylation regulates Hif-1 signaling cascade in activation of hepatic stellate cells[J].Febs Open Bio, 2018, 8 (3) :406-415.
    [5]COPPLE BL, KASKA S, WENTLING C.Hypoxia-inducible factor activation in myeloid cells contributes to the development of liver fibrosis in cholestatic mice[J].J Pharmacol Exp Ther, 2012, 341 (2) :307-316.
    [6]SEMENZA GL, WANG GL.A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation[J].Mol Cell Biol, 1992, 12 (12) :5447-5454.
    [7]KIM Y, NAM HJ, LEE J, et al.Methylation-dependent regulation of HIF-1αstability restricts retinal and tumour angiogenesis[J].Nat Commun, 2016, 7:10347.
    [8]AQUINO-GALVZE A, GONZALEZ-AVILA G, DELGADO-TELLO J, et al.Effects of 2-methoxyestradiol on apoptosis and HIF-1αand HIF-2αexpression in lung cancer cells under normoxia and hypoxia[J].Oncol Rep, 2016, 35 (1) :577-583.
    [9]LIN D, WU J.Hypoxia inducible factor in hepatocellular carcinoma:A therapeutic target[J].World J Gastroenterol, 2015, 21 (42) :12171-12178.
    [10]NATH B, SZABO G.Hypoxia and hypoxia inducible factors:Diverse roles in liver diseases[J].Hepatology, 2012, 55 (2) :622-633.
    [11]ZHAN L, HUANG C, MENG XM, et al.Hypoxia-inducible factor-1alpha in hepatic fibrosis:A promising therapeutic target[J].Biochimie, 2015, 108:1-7.
    [12]MOCHIZUKI A, PACE A, ROCKWELL CE, et al.Hepatic stellate cells orchestrate clearance of necrotic cells in a hypoxiainducible factor-1α-dependent manner by modulating macrophage phenotype in mice[J].J Immunol, 2014, 192 (8) :3847-3857.
    [13]BOZOVA S, ELPEK GO.Hypoxia-inducible factor-1αexpression in experimental cirrhosis:Correlation with vascular endothelial growth factor expression and angiogenesis[J].Apmis, 2010, 115 (7) :795-801.
    [14]MESARWI OA, MI-KYUNG S, SHANNON BF, et al.Hepatocyte hypoxia inducible factor-1 mediates the development of liver fibrosis in a mouse model of nonalcoholic fatty liver disease[J].PLo S One, 2016, 11 (12) :e0168572.
    [15]MOCZYDLOWSKA J, MILTYK W, HERMANOWICZ A, et al.HIF-1αas a key factor in bile duct ligation-induced liver fibrosis in rats[J].J Invest Surg, 2017, 30 (1) :6.
    [16]COPPLE BL, BAI S, BURGOON LD, et al.Hypoxia-inducible factor-1 regulates the expression of genes in hypoxic hepatic stellate cells important for collagen deposition and angiogenesis[J].Liver Int, 2011, 31 (2) :230-244.
    [17] WANG Y, HUANG Y, GUAN F, et al.Hypoxia-inducible factor-1alpha and MAPK co-regulate activation of hepatic stellate cells upon hypoxia stimulation[J].PLo S One, 2013, 8 (9) :e74051.
    [18]COPPLE BL, BUSTAMANTE JJ, WELCH TP, et al.Hypoxiainducible factor-dependent production of profibrotic mediators by hypoxic hepatocytes[J].Liver Int, 2009, 29 (7) :1010-1021.
    [19]ROSMORDUC O, HOUSSET C.Hypoxia:A link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease[J].Semin Liver Dis, 2010, 30 (3) :258-270.
    [20]FABREGAT I, MORENO-CACERES J, SANCHEZ A, et al.TGF-βsignalling and liver disease[J].Febs J, 2016, 283 (12) :2219-2232.
    [21]KIM MJ, PARK SA, KIM CH, et al.TGF-βtypeⅠreceptor kinase inhibitor EW-7197 suppresses cholestatic liver fibrosis by inhibiting HIF1α-induced epithelial mesenchymal transition[J].Cell Physiol Biochem, 2016, 38 (2) :571-588.
    [22]WANG R, ZHANG H, WANG Y, et al.Inhibitory effects of quercetin on the progression of liver fibrosis through the regulation of NF-кB/IкBα, p38 MAPK, and Bcl-2/Bax signaling[J].Int Immunopharmacol, 2017, 47:126-133.
    [23]WANG Y, HUNG Y, GUAN F, et al.Hypoxia-inducible factor-1alpha and MAPK co-regulate activation of hepatic stellate cells upon hypoxia stimulation[J].PLo S One, 2013, 8 (9) :e74051.
    [24]WENG DD, WANG JB, LI GX.Mechanism of PI3K/AKT/m TORsignaling pathway on apoptosis of hepatocyte induced by GCDC[J].Chin J Clin Pharmacol Ther, 2019, 24 (2) :121-127. (in Chinese) 翁丹丹, 王俊波, 郦光晓.PI3K/AKT/m TOR信号通路对甘氨鹅脱氧胆酸钠诱导的肝细胞凋亡的机制研究[J].中国临床药理学与治疗学, 2019, 24 (2) :121-127.
    [25]ZHAO Y, MA X, WANG J, et al.Paeoniflorin alleviates liver fibrosis by inhibiting HIF-1αthrough m TOR-dependent pathway[J].Fitoterapia, 2014, 99:318-327.
    [26]LEE TY, LEU YL, WEN CK.Modulation of HIF-1αand STAT3signaling contributes to anti-angiogenic effect of YC-1 in mice with liver fibrosis[J].Oncotarget, 2017, 8 (49) :86206-86216.
    [27]COPPLE BL.Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor and dependent mechanisms[J].Liver Int, 2010, 30 (5) :669-682.
    [28]DENG J, HUANG Q, WANG Y, et al.Hypoxia-inducible factor-1alpha regulates autophagy to activate hepatic stellate cells[J].Biochem Biophys Res Commun, 2014, 454 (2) :328-334.
    [29]ZHOU YN, SUN MY, MU YP, et al.Xuefuzhuyu decoction inhibition of angiogenesis attenuates liver fibrosis induced by CCl4 in mice[J].J Ethnopharmacol, 2014, 153 (3) :659-666.
    [30]GAO JH, WEN SL, YANG WJ, et al.Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis[J].PLo S One, 2013, 8 (7) :e69309.
    [31]YAO Q, LIN Y, LI X, et al.Curcumin ameliorates intrahepatic angiogenesis and capillarization of the sinusoids in carbon tetrachloride-induced rat liver fibrosis[J].Toxicol Lett, 2013, 222 (1) :72-82.
    [32]TADAKAWA M, TAKEDA T, LI B, et al.The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1αsignaling pathway in ELT-3 cells[J].Mol Cell Endocrinol, 2015, 399:1-8.
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