Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central
    • Subject Terms:
      Apoptosis/*physiology ; Autophagy/*physiology ; Inflammation/*pathology ; Mesenchymal Stem Cells/*pathology ; Stem Cell Niche/*physiology; Animals ; Apoptosis/immunology ; Apoptosis Regulatory Proteins/antagonists & inhibitors ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/immunology ; Autophagy/immunology ; Beclin-1 ; Cytokines/metabolism ; Gene Knockdown Techniques ; Inflammation/immunology ; Inflammation/therapy ; Inflammation Mediators/metabolism ; MAP Kinase Signaling System ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/immunology ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; Sepsis/immunology ; Sepsis/pathology ; Stem Cell Niche/genetics ; Stem Cell Niche/immunology
    • Abstract:
      Background: Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified.
      Methods: We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs.
      Results: Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway.
      Conclusions: Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.
    • References:
      Cancer Cell. 2006 Jul;10(1):51-64. (PMID: 16843265)
      Arthritis Rheum. 2007 Apr;56(4):1175-86. (PMID: 17393437)
      Nature. 2007 Jun 28;447(7148):1121-5. (PMID: 17589504)
      Nature. 2008 Feb 28;451(7182):1069-75. (PMID: 18305538)
      Cell Stem Cell. 2008 Feb 7;2(2):141-50. (PMID: 18371435)
      J Cell Sci. 2008 Apr 15;121(Pt 8):1183-92. (PMID: 18349077)
      Nat Med. 2009 Jan;15(1):42-9. (PMID: 19098906)
      Nat Rev Immunol. 2008 Sep;8(9):726-36. (PMID: 19172693)
      Cell Death Differ. 2009 Mar;16(3):368-77. (PMID: 18846109)
      Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2770-5. (PMID: 19196953)
      Glia. 2009 Aug 15;57(11):1192-203. (PMID: 19191336)
      Antioxid Redox Signal. 2009 Apr;11(4):777-90. (PMID: 18828708)
      J Biol Chem. 2010 Jul 16;285(29):22576-91. (PMID: 20452972)
      Cell Res. 2011 Jan;21(1):103-15. (PMID: 21187859)
      Trends Biochem Sci. 2011 Jan;36(1):30-8. (PMID: 20728362)
      Annu Rev Pathol. 2011;6:457-78. (PMID: 21073342)
      J Exp Med. 2011 Mar 14;208(3):519-33. (PMID: 21282379)
      Trends Microbiol. 2011 Apr;19(4):198-208. (PMID: 21296575)
      Science. 2011 Jul 8;333(6039):228-33. (PMID: 21617041)
      Nat Med. 2011 Dec;17(12):1594-601. (PMID: 22101767)
      Trends Immunol. 2012 Mar;33(3):136-43. (PMID: 22227317)
      Nat Rev Immunol. 2012 May;12(5):383-96. (PMID: 22531326)
      Am J Physiol Lung Cell Mol Physiol. 2012 May 15;302(10):L1003-13. (PMID: 22427530)
      J Clin Invest. 2009 Oct;119(10):3089-101. (PMID: 19729834)
      J Biol Chem. 2012 Sep 28;287(40):33720-32. (PMID: 22879597)
      Am J Pathol. 2012 Nov;181(5):1681-92. (PMID: 23083833)
      Stem Cells. 2013 Feb;31(2):397-407. (PMID: 23132816)
      Cell Stem Cell. 2013 Oct 3;13(4):392-402. (PMID: 24094322)
      Shock. 2013 Nov;40(5):352-7. (PMID: 24088992)
      J Vis Exp. 2014;(84):e51066. (PMID: 24561344)
      Immunity. 2014 Apr 17;40(4):463-75. (PMID: 24745331)
      Autophagy. 2014 Jul;10(7):1301-15. (PMID: 24905997)
      Nat Commun. 2014;5:4710. (PMID: 25134989)
      Stem Cells. 2015 Feb;33(2):615-21. (PMID: 25263397)
      Science. 2004 Jun 4;304(5676):1500-2. (PMID: 15131264)
      Cancer Res. 1998 Aug 1;58(15):3202-8. (PMID: 9699642)
      Blood. 2005 Feb 15;105(4):1815-22. (PMID: 15494428)
      Blood. 2006 Feb 15;107(4):1484-90. (PMID: 16239427)
    • Accession Number:
      0 (Apoptosis Regulatory Proteins)
      0 (Beclin-1)
      0 (Becn1 protein, mouse)
      0 (Cytokines)
      0 (Inflammation Mediators)
      0 (Reactive Oxygen Species)
    • Publication Date:
      Date Created: 20151217 Date Completed: 20160722 Latest Revision: 20181202
    • Publication Date:
      20231215
    • Accession Number:
      PMC4681177
    • Accession Number:
      10.1186/s13287-015-0245-4
    • Accession Number:
      26670667