Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis.

The American Journal of Pathology
Anna MolesM Marí

Abstract

The mechanisms linking hepatocellular death, hepatic stellate cell (HSC) activation, and liver fibrosis are largely unknown. Here, we investigate whether acidic sphingomyelinase (ASMase), a known regulator of death receptor and stress-induced hepatocyte apoptosis, plays a role in liver fibrogenesis. We show that selective stimulation of ASMase (up to sixfold), but not neutral sphingomyelinase, occurs during the transdifferentiation/activation of primary mouse HSCs into myofibroblast-like cells, coinciding with cathepsin B (CtsB) and D (CtsD) processing. ASMase inhibition or genetic down-regulation by small interfering RNA blunted CtsB/D processing, preventing the activation and proliferation of mouse and human HSCs (LX2 cells). In accordance, HSCs from heterozygous ASMase mice exhibited decreased CtsB/D processing, as well as lower levels of alpha-smooth muscle actin expression and proliferation. Moreover, pharmacological CtsB inhibition reproduced the antagonism of ASMase in preventing the fibrogenic properties of HSCs, without affecting ASMase activity. Interestingly, liver fibrosis induced by bile duct ligation or carbon tetrachloride administration was reduced in heterozygous ASMase mice compared with that in wild-type anim...Continue Reading

References

Mar 15, 1981·Analytical Biochemistry·I S JamallS S Que Hee
Nov 10, 1995·The Journal of Biological Chemistry·P Liu, R G Anderson
Oct 3, 1999·The EMBO Journal·M HeinrichS Schütze
Mar 30, 2001·The Journal of Biological Chemistry·H GrassmeE Gulbins
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 18, 2003·The Journal of Clinical Investigation·Carmen García-RuizJosé C Fernández-Checa
Jun 12, 2003·JAMA : the Journal of the American Medical Association·Jeanne M Clark, Anna Mae Diehl
Jul 17, 2003·The Journal of Clinical Investigation·Ali CanbayGregory J Gores
Aug 23, 2003·Oncogene·Heike GrassméErich Gulbins
Jan 24, 2004·Cell Death and Differentiation·M HeinrichS Schütze
Apr 16, 2004·Seminars in Liver Disease·Elizabeth M Brunt
Feb 4, 2005·The Journal of Clinical Investigation·Ramón Bataller, David A Brenner
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Sep 6, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Shigeki TsukadaRichard A Rippe
Aug 31, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Laura LlacunaAlbert Morales
Sep 9, 2006·Journal of Gastroenterology and Hepatology·Tatiana Kisseleva, David A Brenner
Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Albert MoralesJosé C Fernandez-Checa
Mar 3, 2007·The Journal of Clinical Investigation·John P Iredale
Jul 17, 2007·Journal of Inherited Metabolic Disease·E H Schuchman
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid
Feb 5, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Yu LiuMyles C Cabot
Jun 24, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eric L Smith, Edward H Schuchman
Jul 17, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Eric L Smith, Edward H Schuchman
Aug 30, 2008·Sub-cellular Biochemistry·Katrin Anne BeckerErich Gulbins
Dec 17, 2008·Journal of Lipid Research·Sandra K Erickson
Jan 1, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna MolesMontserrat Marí
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yosuke OsawaMasahito Nagaki

❮ Previous
Next ❯

Citations

Jul 19, 2013·Annual Review of Nutrition·E Scorletti, C D Byrne
Nov 11, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Rajwinder DhamiEdward H Schuchman
Jan 23, 2016·Nature Reviews. Drug Discovery·Giovanni MussoRoberto Gambino
May 7, 2014·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Ralph C QuillinAlex B Lentsch
Nov 30, 2012·Journal of Cellular Biochemistry·Wu-Yi SunWei Wei
Apr 28, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Núria TarratsMontserrat Marí
Jul 28, 2011·Alcoholism, Clinical and Experimental Research·Mashiko SetshediSuzanne M de la Monte
Oct 5, 2014·Journal of Hepatology·Carmen Garcia-RuizJosé C Fernández-Checa
Oct 30, 2015·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Liu YangJun-Ying Zhou
Apr 29, 2014·Biochimica Et Biophysica Acta·Georgios GrammatikosJosef Pfeilschifter
Feb 11, 2015·Apoptosis : an International Journal on Programmed Cell Death·Cristiana PerrottaEmilio Clementi
Sep 7, 2011·The American Journal of Pathology·Krishna M BoiniPin-Lan Li
Nov 11, 2016·Cell Death & Disease·Álvaro de MingoMontserrat Marí
Apr 20, 2017·International Journal of Molecular Sciences·Ha-Yeun ChungRalf A Claus
Nov 11, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Li ZhangQiang Wang
Jan 13, 2018·Journal of Neural Transmission·Liubov S KalinichenkoChristian P Müller
Jun 16, 2017·Clinical and Translational Gastroenterology·Mansi ManchandaShyam S Chauhan
Mar 12, 2019·Clinical and Experimental Pharmacology & Physiology·Xingxing MengJunxiang Bao
Dec 22, 2019·International Journal of Molecular Sciences·Jorge SimonMaría Luz Martínez-Chantar
Jun 6, 2020·The Journal of Infectious Diseases·Susanna NaggieKeyur Patel
Sep 3, 2014·Biological Chemistry·Gilles LalmanachMariana Kasabova
Mar 18, 2015·Biological Chemistry·Hiroyuki NojimaAlex B Lentsch
Nov 22, 2011·The Journal of Biological Chemistry·Anna MolesMontserrat Marí
Jan 25, 2017·Future Science OA·Aniruddha AdhikariSamir Kumar Pal
Sep 13, 2017·Particle and Fibre Toxicology·Rupa BiswasAndrij Holian
Jun 16, 2018·Scientific Reports·Othman SoufanVladimir B Bajic
Jun 4, 2020·International Journal of Molecular Sciences·Estefanía de GregorioMontserrat Marí
Aug 1, 2020·BioMed Research International·Ke PeiYunlun Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.