Comparison of Carotenoids for Their Antifibrogenic Effects in Hepatic Stellate Cells.
Astaxanthin
Carotenoids
Fibrogenesis
Hepatic stellate cell
Lutein
Journal
Lipids
ISSN: 1558-9307
Titre abrégé: Lipids
Pays: United States
ID NLM: 0060450
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
16
02
2019
revised:
28
04
2019
accepted:
01
05
2019
pubmed:
30
5
2019
medline:
6
2
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
Hepatic stellate cells (HSC) have an important role in the development of liver fibrosis by producing extracellular matrix proteins when they are activated upon liver injury. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, attenuates HSC activation. The objective of this study was to compare the anti-fibrogenic effects of ASTX with those of other common carotenoids. LX-2 cells, a human HSC cell line, were treated with ASTX, lycopene, lutein (LT), zeaxanthin, or canthaxanthin, to measure messenger RNA (mRNA) and protein expression of pro-fibrogenic genes. Pro-fibrogenic gene expressions were also measured in ASTX- or LT-treated primary mouse HSC. To determine the underlying mechanisms of the anti-fibrogenic effect of ASTX and LT, SMA-related and MAD-related protein 3 (SMAD3) pathways and the accumulation of reactive oxygen species (ROS) were measured in LX-2 cells. Among five carotenoids tested, ASTX and LT attenuated HSC activation in LX-2 cells by reducing the mRNA and protein levels of pro-fibrogenic genes, such as smooth muscle α actin and procollagen type I α1 (COL1A1). In addition, both ASTX and LT significantly decreased the expression of pro-fibrogenic genes, including COL1A1, COL3A1, and COL6A1, in activated primary mouse HSC, with ASTX being more potent than LT. The anti-fibrogenic effect of ASTX was mediated by inhibiting the phosphorylation of SMAD3 and cellular ROS accumulation, while LT only prevented the accumulation of ROS in LX-2 cells. In conclusion, ASTX showed the most potent anti-fibrogenic effect among the five carotenoids via inhibition of SMAD3 phosphorylation and cellular ROS accumulation while LT only prevented ROS levels in HSC.
Identifiants
pubmed: 31140624
doi: 10.1002/lipd.12157
pmc: PMC6591040
mid: NIHMS1035851
doi:
Substances chimiques
Reactive Oxygen Species
0
Carotenoids
36-88-4
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-410Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK108254
Pays : United States
Informations de copyright
© 2019 AOCS.
Références
Liver Int. 2006 Feb;26(1):8-22
pubmed: 16420505
Gastroenterology. 2010 Jun;138(7):2509-18, 2518.e1
pubmed: 20230822
J Pathol. 2013 Jan;229(2):298-309
pubmed: 22996908
J Nutr. 2008 Mar;138(3):476-81
pubmed: 18287352
J Clin Invest. 2005 Feb;115(2):209-18
pubmed: 15690074
Am J Pathol. 1998 Aug;153(2):527-35
pubmed: 9708812
Nat Rev Immunol. 2014 Mar;14(3):181-94
pubmed: 24566915
Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):195-206
pubmed: 21497738
Gastroenterology. 2002 May;122(5):1303-13
pubmed: 11984517
Am J Physiol Gastrointest Liver Physiol. 2000 Aug;279(2):G245-9
pubmed: 10915630
Biochim Biophys Acta. 2007 Jan;1768(1):167-74
pubmed: 17070769
J Hepatol. 2004 Jan;40(1):60-8
pubmed: 14672615
Compr Physiol. 2013 Oct;3(4):1473-92
pubmed: 24265236
Biochim Biophys Acta. 2015 Jan;1850(1):178-85
pubmed: 25450180
Arch Biochem Biophys. 1992 Sep;297(2):291-5
pubmed: 1497349
Br J Nutr. 2014 Dec 14;112(11):1797-804
pubmed: 25328157
Hepatology. 2002 Jan;35(1):62-73
pubmed: 11786960
J Invest Dermatol. 2002 Feb;118(2):211-5
pubmed: 11841535
Am J Anat. 1971 Dec;132(4):429-62
pubmed: 4942297
J Nutr Biochem. 2017 Feb;40:172-177
pubmed: 27915160
Biochim Biophys Acta. 2005 May 30;1740(2):108-15
pubmed: 15949676
Nutr Res Pract. 2012 Apr;6(2):113-9
pubmed: 22586499
Physiol Rev. 2008 Jan;88(1):125-72
pubmed: 18195085
Nutr Res. 2008 Feb;28(2):83-91
pubmed: 19083393
Int J Clin Exp Med. 2015 Jun 15;8(6):8785-93
pubmed: 26309530
Fibrogenesis Tissue Repair. 2009 Apr 02;2(1):2
pubmed: 19341455
J Nutr Biochem. 2017 May;43:27-35
pubmed: 28193580
Annu Rev Pathol. 2011;6:425-56
pubmed: 21073339
Dig Dis Sci. 2009 Jul;54(7):1460-4
pubmed: 19424798
Front Biosci (Landmark Ed). 2012 Jun 01;17:2495-507
pubmed: 22652794
Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30
pubmed: 22992590
Mol Cell Biochem. 2008 Oct;317(1-2):43-50
pubmed: 18581202
Biol Pharm Bull. 2002 Mar;25(3):390-2
pubmed: 11913541
Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):397-411
pubmed: 28487545
Hepatology. 2017 Mar;65(3):1039-1043
pubmed: 27859502
Histol Histopathol. 2009 Jul;24(7):893-900
pubmed: 19475535
FASEB J. 1995 Dec;9(15):1551-8
pubmed: 8529834
Biochim Biophys Acta. 2001 Jun 6;1512(2):251-8
pubmed: 11406102
J Nat Prod. 2006 Mar;69(3):443-9
pubmed: 16562856
Hepatology. 2004 Jun;39(6):1647-54
pubmed: 15185306
Am J Cardiol. 2008 May 22;101(10A):58D-68D
pubmed: 18474276
Nutrients. 2014 Jan 27;6(2):466-88
pubmed: 24473231
J Nutr Biochem. 2016 Mar;29:21-6
pubmed: 26895661
Hepatology. 2001 Jul;34(1):89-100
pubmed: 11431738
Mediators Inflamm. 2014;2014:954502
pubmed: 24860243
Eur J Nutr. 2015 Sep;54(6):933-44
pubmed: 25241023
Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1836-43
pubmed: 15550525
J Nutr. 2011 Sep;141(9):1611-7
pubmed: 21734060
Cell Tissue Res. 2012 Jan;347(1):245-56
pubmed: 22006249
Mol Aspects Med. 2003 Dec;24(6):345-51
pubmed: 14585305
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
Recent Pat Food Nutr Agric. 2012 Aug;4(2):91-106
pubmed: 22594662
Vet Med Int. 2010 Oct 03;2010:
pubmed: 20953409
Semin Liver Dis. 2015 May;35(2):107-18
pubmed: 25974897
J Nutr Biochem. 2012 Oct;23(10):1201-6
pubmed: 22819548
J Nutr Biochem. 2013 Nov;24(11):1870-81
pubmed: 23972952