Cathepsin B deficiency ameliorates liver lipid deposition, inflammatory cell infiltration, and fibrosis after diet-induced nonalcoholic steatohepatitis.

Szczegóły
Abstrakt

Tytuł:: Cathepsin B deficiency ameliorates liver lipid deposition, inflammatory cell infiltration, and fibrosis after diet-induced nonalcoholic steatohepatitis.
Autorzy:: Fang W; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.
Deng Z; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Geriatrics, National Key Clinic Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Benadjaoud F; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Yang C; Department of Geriatrics, National Key Clinic Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China. Electronic address: .
Shi GP; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: .
Źródło:: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2020 Aug; Vol. 222, pp. 28-40. Date of Electronic Publication: 2020 May 11.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: New York, N.Y. : Elsevier, [2006]-
MeSH Terms:: Diet, High-Fat*
Lipid Metabolism*
Cathepsin B/*deficiency
Inflammation/*pathology
Liver/*metabolism
Liver Cirrhosis/*complications
Liver Cirrhosis/*enzymology
Non-alcoholic Fatty Liver Disease/*complications
Animals ; Cadherins ; Cathepsin B/metabolism ; Cell Polarity ; Liver/pathology ; Liver/physiopathology ; Liver Cirrhosis/physiopathology ; Macrophages/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/enzymology ; Non-alcoholic Fatty Liver Disease/physiopathology ; Signal Transduction ; Smad Proteins/metabolism ; Transforming Growth Factor beta/metabolism ; Weight Gain
References:: World J Gastroenterol. 2008 Jan 14;14(2):185-92. (PMID: 18186553)
J Biol Chem. 1994 Apr 15;269(15):11530-6. (PMID: 8157683)
Biomed Rep. 2014 Sep;2(5):633-636. (PMID: 25054002)
Gut. 2011 Oct;60(10):1394-402. (PMID: 21270117)
Hepatology. 2009 Apr;49(4):1297-307. (PMID: 19116891)
Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):319-33. (PMID: 21497748)
J Mol Neurosci. 2001 Apr-Jun;16(2-3):117-21; discussion 151-7. (PMID: 11478366)
Res Commun Chem Pathol Pharmacol. 1992 Apr;76(1):95-112. (PMID: 1518964)
Am J Pathol. 2007 Jun;170(6):1807-16. (PMID: 17525249)
Cleve Clin J Med. 2008 Oct;75(10):721-8. (PMID: 18939388)
J Biol Chem. 2002 Aug 9;277(32):28669-76. (PMID: 12039963)
Dig Dis Sci. 2014 Jul;59(7):1617-24. (PMID: 24464211)
Cell Mol Immunol. 2012 Jul;9(4):296-301. (PMID: 22157623)
Curr Pharm Des. 2007;13(21):2193-8. (PMID: 17627552)
J Clin Invest. 2000 Nov;106(9):1127-37. (PMID: 11067865)
Eur J Clin Chem Clin Biochem. 1996 Jul;34(7):555-60. (PMID: 8864404)
J Hepatol. 2012 Apr;56(4):952-64. (PMID: 22173168)
Int J Mol Sci. 2013 Jun 05;14(6):11963-80. (PMID: 23739675)
J Biol Chem. 2014 Jun 6;289(23):16239-51. (PMID: 24790080)
Nat Rev Cardiol. 2018 Jun;15(6):351-370. (PMID: 29679024)
J Nutr Biochem. 2011 Jun;22(6):527-34. (PMID: 20801629)
Trends Endocrinol Metab. 2009 Mar;20(2):72-7. (PMID: 19185504)
Cell Metab. 2016 Dec 13;24(6):848-862. (PMID: 28068223)
Eur J Intern Med. 2008 Mar;19(2):75-82. (PMID: 18249301)
Hepatol Res. 2005 Oct;33(2):68-71. (PMID: 16214395)
Hepatology. 2018 Jan;67(1):328-357. (PMID: 28714183)
J Lipid Res. 2009 Apr;50 Suppl:S412-6. (PMID: 19074370)
iScience. 2019 Sep 27;19:607-622. (PMID: 31446224)
Biochem Biophys Res Commun. 1998 Oct 9;251(1):379-87. (PMID: 9790964)
J Am Heart Assoc. 2019 Jul 16;8(14):e011994. (PMID: 31296090)
Sci Rep. 2017 Mar 16;7:44612. (PMID: 28300213)
Endocrinology. 2016 Feb;157(2):570-85. (PMID: 26650570)
Nat Rev Immunol. 2010 Mar;10(3):210-5. (PMID: 20168318)
J Hepatol. 2008 Jun;48(6):983-92. (PMID: 18395289)
Tumori. 2013 Jan-Feb;99(1):10-6. (PMID: 23548993)
Hypertension. 2005 May;45(5):1012-8. (PMID: 15824194)
Prostaglandins Other Lipid Mediat. 2006 Sep;80(3-4):165-74. (PMID: 16939881)
J Clin Gastroenterol. 2006 Mar;40 Suppl 1:S5-10. (PMID: 16540768)
J Hepatol. 2019 Nov;71(5):1012-1021. (PMID: 31301321)
J Clin Invest. 2003 Jul;112(2):152-9. (PMID: 12865404)
J Biol Chem. 2004 Feb 13;279(7):5470-9. (PMID: 14645229)
J Biol Chem. 2012 Jan 6;287(2):1178-88. (PMID: 22102288)
FEBS J. 2015 Nov;282(22):4328-40. (PMID: 26306868)
Circulation. 2007 Apr 17;115(15):2065-75. (PMID: 17404153)
Metab Syndr Relat Disord. 2008 Mar;6(1):1-7. (PMID: 18370830)
Gastroenterology. 2010 Jun;138(7):2477-86, 2486.e1-3. (PMID: 20206177)
Hepatology. 2009 Oct;50(4):1094-104. (PMID: 19637282)
Oncology. 1997 Jan-Feb;54(1):79-83. (PMID: 8978598)
Grant Information:: R01 AG063839 United States AG NIA NIH HHS; R01 HL060942 United States HL NHLBI NIH HHS; R01 HL123568 United States HL NHLBI NIH HHS; R56 AG058670 United States AG NIA NIH HHS
Substance Nomenclature:: 0 (Cadherins)
0 (Smad Proteins)
0 (Transforming Growth Factor beta)
EC 3.4.22.1 (Cathepsin B)
Entry Date(s):: Date Created: 20200522 Date Completed: 20200923 Latest Revision: 20210802
Update Code:: 20240105
PubMed Central ID:: PMC7311307
DOI:: 10.1016/j.trsl.2020.04.011
PMID:: 32434697
: Czasopismo naukowe

Full Text Finder

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease characterized by fat accumulation and inflammation in liver. Yet, the mechanistic insight and diagnostic and therapeutic options of NASH remain incompletely understood. This study tested the roles of cysteine protease cathepsin B (CatB) in mouse NASH development. Immunoblot revealed increased liver CatB expression in NASH mice. Fructose-palmitate-cholesterol diet increased body weight gain, liver to body weight ratio, blood fasting glucose, plasma total cholesterol and alanine transaminase levels, and liver triglyceride, but decreased plasma high-density lipoprotein in wild-type mice. All these changes were blunted in CatB-deficient (Ctsb -/- ) mice. In parallel to reduced expression of genes involved in liver lipid transport and lipogenesis, liver CD36, FABP4, and PPARγ protein levels were also significantly decreased in Ctsb -/- mice, although CatB deficiency did not affect liver gluconeogenesis and fatty acid beta-oxidation-associated gene expression. Mechanistic studies showed that CatB deficiency decreased liver expression of adhesion molecules, inflammatory cytokine, and chemokine, along with reduced liver inflammatory cell infiltration. CatB deficiency also promoted M2 macrophage polarization and reduced liver TGF-β1 signaling and fibrosis. Together, CatB deficiency improves liver function in NASH mice by suppressing de novo lipogenesis and liver inflammation and fibrosis.
(Copyright © 2020 Elsevier Inc. All rights reserved.)

Informacja