Einzeltreffer — DigiBib

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease [NAFLD]) and metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis [NASH]) are leading chronic liver diseases, driving cirrhosis, hepatocellular carcinoma, and mortality. MASLD/MASH is associated with increased senescence proteins, including Activin A, and senolytics have been proposed as a therapeutic approach. To test the role of Activin A, we induced hepatic expression of Activin A in a murine MASLD/MASH model. Surprisingly, overexpression of hepatic Activin A dramatically mitigated MASLD, reducing liver steatosis and inflammation as well as systemic fat accumulation, while improving insulin sensitivity. Further studies identified a dramatic decrease in the lipid-associated macrophages marker glycoprotein NMB (Gpnmb) by Activin A, and Gpnmb knockdown in the same model produced similar benefits and transcriptional changes to Activin A expression. These studies reveal a surprising protective role for Activin A in MASLD and the potential for SASP proteins to have context-specific beneficial effects. Moreover, they implicate both Activin A and Gpnmb as potential therapeutic targets for this condition.

Titel:	Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
Autor/in / Beteiligte Person:	Liu, H ; Yerevanian, A ; Westerhoff, M ; Hastings, MH ; Guerra, JRB ; Zhao, M ; Svensson, KJ ; Cai, B ; Soukas, AA ; Rosenzweig, A
Zeitschrift:	Diabetes, Jg. 73 (2024-02-01), Heft 2, S. 260-279
Veröffentlichung:	Alexandria, VA : American Diabetes Association ; <i>Original Publication</i>: [New York, American Diabetes Association], 2024
Medientyp:	academicJournal
ISSN:	1939-327X (electronic)
DOI:	10.2337/db23-0357
Schlagwort:	Animals Mice Eye Proteins Membrane Glycoproteins genetics Transcription Factors Activins genetics Activins metabolism Metabolic Diseases Non-alcoholic Fatty Liver Disease
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Diabetes] 2024 Feb 01; Vol. 73 (2), pp. 260-279. MeSH Terms: Activins* / genetics ; Activins* / metabolism ; Metabolic Diseases* ; Non-alcoholic Fatty Liver Disease* ; Animals ; Mice ; Eye Proteins ; Membrane Glycoproteins / genetics ; Transcription Factors References: Gastroenterology. 2011 Oct;141(4):1249-53. (PMID: 21726509) ; Nat Rev Nephrol. 2016 Jun;12(6):325-38. (PMID: 27108839) ; JAMA. 2020 Mar 24;323(12):1175-1183. (PMID: 32207804) ; Hepatology. 2019 May;69(5):2241-2257. (PMID: 30372785) ; Cell Rep. 2018 Oct 30;25(5):1193-1203. (PMID: 30380411) ; Nat Commun. 2017 Jun 13;8:15691. (PMID: 28608850) ; Am J Gastroenterol. 2018 Nov;113(11):1649-1659. (PMID: 29880964) ; Signal Transduct Target Ther. 2022 Aug 13;7(1):287. (PMID: 35963848) ; JCI Insight. 2020 Jun 18;5(12):. (PMID: 32554926) ; Am J Gastroenterol. 2009 Sep;104(9):2196-205. (PMID: 19532130) ; Nat Rev Gastroenterol Hepatol. 2021 Mar;18(3):151-166. (PMID: 33128017) ; Hepatology. 2012 Jul;56(1):95-107. (PMID: 22278400) ; Annu Rev Pathol. 2010;5:99-118. (PMID: 20078217) ; Arterioscler Thromb Vasc Biol. 2012 May;32(5):1094-8. (PMID: 22517368) ; Hepatology. 2020 Jan;71(1):363-374. (PMID: 31230380) ; J Hepatol. 2017 Aug;67(2):349-359. (PMID: 28365312) ; Oncogene. 2002 Mar 28;21(14):2227-35. (PMID: 11948405) ; Nat Rev Endocrinol. 2019 Dec;15(12):689-700. (PMID: 31554932) ; Sci Transl Med. 2019 Mar 6;11(482):. (PMID: 30842316) ; Gut. 2020 Jun;69(6):1104-1115. (PMID: 31767630) ; Cell Metab. 2016 Dec 13;24(6):848-862. (PMID: 28068223) ; J Clin Invest. 2002 Mar;109(5):595-601. (PMID: 11877467) ; J Transl Med. 2019 Dec 17;17(1):422. (PMID: 31847906) ; Cell. 2008 Aug 22;134(4):657-67. (PMID: 18724938) ; Atherosclerosis. 2014 Nov;237(1):200-7. (PMID: 25244504) ; PLoS Biol. 2020 Jan 16;18(1):e3000599. (PMID: 31945054) ; Cell Metab. 2007 Jul;6(1):38-54. (PMID: 17618855) ; Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):. (PMID: 33811139) ; Sci Rep. 2015 Nov 19;5:16920. (PMID: 26581806) ; Hepatol Commun. 2022 Oct;6(10):2812-2826. (PMID: 35866567) ; Sci Transl Med. 2022 Nov 23;14(672):eabp8309. (PMID: 36417485) ; Int J Biol Sci. 2018 Aug 6;14(11):1483-1496. (PMID: 30263000) ; Hepatology. 2024 Feb 1;79(2):409-424. (PMID: 37505219) ; iScience. 2022 Dec 15;26(1):105802. (PMID: 36636354) ; Nat Metab. 2019 May;1(5):570-583. (PMID: 32694855) ; Arterioscler Thromb Vasc Biol. 2023 Feb;43(2):330-349. (PMID: 36453275) ; Nat Commun. 2022 Aug 16;13(1):4827. (PMID: 35974106) ; J Biol Chem. 2021 Nov;297(5):101232. (PMID: 34582891) ; J Hepatol. 2011 Sep;55(3):654-659. (PMID: 21172393) ; Nat Cell Biol. 2002 May;4(5):E131-6. (PMID: 11988758) ; Nat Rev Drug Discov. 2016 Apr;15(4):249-74. (PMID: 26794269) ; Cell Commun Signal. 2021 Apr 8;19(1):44. (PMID: 33832488) ; Sci Adv. 2020 Nov 27;6(48):. (PMID: 33246954) ; N Engl J Med. 2017 Nov 23;377(21):2063-2072. (PMID: 29166236) ; Mol Cell. 2019 Aug 8;75(3):644-660.e5. (PMID: 31398325) ; Metabolism. 2016 Oct;65(10):1550-8. (PMID: 27621190) ; Elife. 2015 Dec 19;4:e12997. (PMID: 26687007) Grant Information: 23IPA1042031 United States AHA American Heart Association-American Stroke Association; R01 DK125260 United States DK NIDDK NIH HHS; K99AR081618 United States NH NIH HHS; R01 HL167107 United States HL NHLBI NIH HHS; R35 HL155318 United States HL NHLBI NIH HHS; P30 DK116074 United States DK NIDDK NIH HHS; R35 GM147269 United States GM NIGMS NIH HHS; R01 DK134610 United States DK NIDDK NIH HHS; R01 AG061034 United States AG NIA NIH HHS; P30 DK040561 United States DK NIDDK NIH HHS; K99 AR081618 United States AR NIAMS NIH HHS Substance Nomenclature: 0 (activin A) ; 104625-48-1 (Activins) ; 0 (Eye Proteins) ; 0 (Gpnmb protein, mouse) ; 0 (Membrane Glycoproteins) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20231107 Date Completed: 20240130 Latest Revision: 20240210 Update Code: 20240210 PubMed Central ID: PMC10796305

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).