Upregulated expression of hypoxia reactive genes in peripheral blood mononuclear cells from chronic liver disease patients.
AM, Adrenomedullin
ANGPTL4, Angiopoietin-like 4
Adrenomedullin
CH, chronic hepatitis
CLD, chronic liver disease
Chronic liver disease
GPx, glutathione peroxidase
HCC, hepatocellular carcinoma
HCV, hepatitis C virus
HIF, hypoxia inducible factor
HO-1, heme oxygenase -1
HV, healthy volunteers
IL-6, Interleukin-6
Intrahepatic hypoxia
LC, liver cirrhosis
LDH, lactate dehydrogenase
MCP-1, Monocyte chemoattractant protein-1
PBMC, Peripheral blood mononuclear cells
PT, prothrombin time
Peripheral blood mononuclear cells
ROS, reactive oxygen species
SOD, Superoxide dismutase
TGF-β, transforming growth factor-beta
TNF-α, Tumor Necrosis Factor-α
VEGF, vascular endothelial growth factor
VEGFA, vascular endothelial growth factor A
VEGFR2, vascular endothelial growth factor receptor 2
Journal
Biochemistry and biophysics reports
ISSN: 2405-5808
Titre abrégé: Biochem Biophys Rep
Pays: Netherlands
ID NLM: 101660999
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
24
03
2020
revised:
30
03
2021
accepted:
28
06
2021
entrez:
26
7
2021
pubmed:
27
7
2021
medline:
27
7
2021
Statut:
epublish
Résumé
Liver fibrosis induces intrahepatic microcirculation disorder and hypoxic stress. Hypoxic stress has the potential for an increase in the possibility of more liver fibrosis and carcinogenesis. Liver biopsy is a standard method that evaluates of intrahepatic hypoxia, however, is invasive and has a risk of bleeding as a complication. Here, we investigated the hypoxia reactive gene expressions in peripheral blood mononuclear cells (PBMC) from chronic liver disease patients to evaluate intrahepatic hypoxia in a non-invasive manner. The subjects enrolled for this study were composed of 20 healthy volunteers (HV) and 48 patients with chronic liver disease (CLD). CLD patients contained 24 patients with chronic hepatitis（CH）and 24 patients with liver cirrhosis (LC). PBMC were isolated from heparinized peripheral blood samples. We measured the transcriptional expression of hypoxia reactive genes and inflammatory cytokines by quantitative RT-PCR. mRNA expression of adrenomedullin (AM), vascular endothelial growth factor A (VEGFA) superoxide dismutase (SOD), glutathione peroxidase (GPx) (p < 0.05), Interleukin-6 (IL-6), transforming growth factor-beta (TGF-β) and heme oxygenase-1 (HO-1) in CLD group were significantly higher than HV. AM mRNA expression is correlated with serum lactate dehydrogenase (LDH), serum albumin (Alb), IL6, and SOD mRNA expression. The hypoxia reactive gene expression in PBMCs from CLD patients was more upregulated than HV. Especially, angiogenic genes were notably upregulated and correlated with liver fibrosis. Here, we suggest that mRNA expression of AM in PBMCs could be the biomarker of intrahepatic hypoxia.
Identifiants
pubmed: 34307908
doi: 10.1016/j.bbrep.2021.101068
pii: S2405-5808(21)00162-X
pmc: PMC8283323
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101068Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
Références
Oncology. 2011;81 Suppl 1:11-7
pubmed: 22212930
Am J Physiol Regul Integr Comp Physiol. 2007 Oct;293(4):R1693-701
pubmed: 17634197
Biochem Biophys Res Commun. 2014 Nov 14;454(2):328-34
pubmed: 25450397
J Hepatol. 1998 May;28(5):840-6
pubmed: 9625320
Hepatology. 2012 Feb;55(2):622-33
pubmed: 22120903
Leuk Lymphoma. 1999 Jun;34(1-2):1-23
pubmed: 10350328
Free Radic Biol Med. 2016 Nov;100:81-85
pubmed: 27296839
Orv Hetil. 2002 Jan 13;143(2):83-6
pubmed: 11868453
Clin Cancer Res. 2005 Feb 1;11(3):1181-9
pubmed: 15709187
World J Hepatol. 2015 Mar 27;7(3):377-91
pubmed: 25848465
Semin Liver Dis. 2010 Aug;30(3):258-70
pubmed: 20665378
Biochem Biophys Res Commun. 1993 Apr 30;192(2):553-60
pubmed: 8387282
J Hepatol. 1998 Aug;29(2):250-6
pubmed: 9722206
Hepatol Int. 2016 Jan;10(1):124-32
pubmed: 26420218
J Hepatol. 1998 Feb;28(2):307-13
pubmed: 9580278
Gastroenterology. 1998 Feb;114(2):336-43
pubmed: 9453495
J Clin Invest. 2010 Aug;120(8):2699-714
pubmed: 20644254
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4273-8
pubmed: 9113979
J Cell Physiol. 2008 Dec;217(3):674-85
pubmed: 18651560
Cancer Res. 2008 Dec 15;68(24):10267-79
pubmed: 19074895
J Hepatol. 1992 Jul;15(3):372-7
pubmed: 1447505
Hepatology. 2002 Jul;36(1):103-11
pubmed: 12085354
Liver Int. 2011 Feb;31(2):146-62
pubmed: 21073649
J Rheumatol. 2009 Jun;36(6):1318-29
pubmed: 19369471
Hepatology. 2011 May;53(5):1526-37
pubmed: 21520168
Dig Dis Sci. 1999 Feb;44(2):372-6
pubmed: 10063925
J Infect Dis. 2007 Jan 15;195(2):255-67
pubmed: 17191171
J Immunol. 2007 Jun 15;178(12):7516-9
pubmed: 17548584
Int J Mol Sci. 2016 Jun 14;17(6):
pubmed: 27314335
Mol Cell. 2010 Oct 22;40(2):294-309
pubmed: 20965423
Microbiol Immunol. 2011 Feb;55(2):130-4
pubmed: 21204953
World J Gastroenterol. 2014 Jul 7;20(25):8082-91
pubmed: 25009380
World J Gastroenterol. 2005 Feb 14;11(6):846-9
pubmed: 15682478
Scand J Gastroenterol. 2004 Jul;39(7):686-93
pubmed: 15370692
Hepatobiliary Pancreat Dis Int. 2006 Nov;5(4):560-3
pubmed: 17085342
BMC Infect Dis. 2015 Dec 04;15:556
pubmed: 26637466
Hepatology. 2002 Nov;36(5):1172-9
pubmed: 12395327
World J Gastroenterol. 1999 Aug;5(4):301-304
pubmed: 11819452
World J Gastroenterol. 2006 Apr 7;12(13):2095-102
pubmed: 16610064
World J Gastroenterol. 2007 Jun 21;13(23):3176-82
pubmed: 17589895
Transplant Proc. 2008 Jul-Aug;40(6):2042-5
pubmed: 18675125
FASEB J. 2003 Jul;17(10):1195-214
pubmed: 12832285
J Cell Physiol. 1997 Dec;173(3):335-42
pubmed: 9369946